The Effect of Morning Versus Evening Administration on The Pharmacokinetics and Pharmacodynamics of Empagliflozin

An Open-label, One way, Two period Comparative study To Determine The effect of Morning Versus Evening administration of Empagliflozin 10mg on Its Pharmacokinetics And Pharmacodynamics in Healthy Adults

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Pharmacokinetics; Pharmacodynamics
• Intervention / Treatment: Drug: Empagliflozin 10 MG Oral Tablet [Jardiance]

Detailed Description

Sixteen(16) healthy subjects will receive a single oral dose of Empagliflozin at the evening(Period I) and after a seven days washout period, the same 16 subjects will receive a single oral dose of Empagliflozin at the morning(Period II).

In both Periods(I and II), blood samples will be collected from each volunteer ethylene diamine tetra-acetic acid(KEDTA) containing tubes prior to drug administration then samples will be obtained at 0.33, 0.67, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours(h) after drug administration.

These samples will be centrifuged and the plasma harvested and stored at -80°C until assay.

Urine samples will be collected over the first 24h after oral administration of the drug with sampling being at the following intervals: 0 to 4h, 4 to 8h, 8-12h, 12 to 24hr.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Drug Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is at least 18-45 years at screening.
• Subject has a Body Mass Index of 18 to 35 kg/m2.
• Subject are non smokers or moderate smokers(not more than 5 cigarettes per day)
• Subject is willing to participate and give their final written consent prior to the commencement of the study procedures
• Subject is in good age-appropriate health condition as established by medical history, physical examination, and results of biochemistry, hematology and urine analysis testing within 4 weeks prior to study.
• Subject has a normal blood pressure and pulse rate, according to the reference normal ranges

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 two weeks preceding of the trial starting date.
• Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
• Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.
• Gastrointestinal diseases.
• Renal diseases.
• Cardiovascular diseases specially transient ischemic attacks and cardiac dysrhythmia .
• Pancreatic disease including diabetes.
• Hepatic diseases as hepatic failure, cirrhosis, galactose intolerance, fructose intolerance, glycogen storage diseases
• Hematological disease or pulmonary disease
• Abnormal laboratory values.
• Subjects who have donated blood or who have been involved in a drug study within 6 weeks preceding the start of the study.
• Positive HIV test.
• History of or current abuse of drugs, alcohol or solvents.
• Endocrine disorders as Pheochromocytoma, Addison disease, glucagon deficiency, carcinomas, extra-hepatic tumors
• Autoimmune disorders as Graves disease
• (Central nervous system (CNS) disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Experimental Arm; Subjects will receive a single oral dose of Empagliflozin 10 MG Oral Tablet [Jardiance]	Drug: Empagliflozin 10 MG Oral Tablet [Jardiance]; Empagliflozin is a sodium-glucose co-transporter 2 inhibitor approved for treatment of type 2 diabetes mellitus; Other Names: Jardiance (Boehringer Ingelheim and Eli Lilly)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum drug concentration in plasma (Cmax)	Maximum drug concentration in plasma measured in (ng/ml)	0 up to 4 hours
Area under the plasma concentration-time curve from time 0 to 48 hours(h) (AUC0→48h)	Area under the plasma concentration-time curve from time 0 to time(t) measured in(ng.h/ml)	From first sampling interval up to 48 hours
Time to Maximum drug concentration in plasma (tmax)	Time corresponding to maximum drug concentration in plasma measured in Hours(h)	0 up to 4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Urinary Glucose Excreted over the first 24 hours (Cumulative UGE)	The Cumulative amount of Glucose excreted in Urine over the first 24 hours after drug administration measured in Milligrams (mg)	From 0 up to 24 hours
Half life( t½) of drug in plasma	Half life of drug measured in Hours(hr)	Up to 48 hours

Collaborators and Investigators

• Sponsor: Ain Shams University
• Collaborators: Drug Research Centre, Cairo, Egypt
• Investigators: Principal Investigator: Rana M Ali, MD student, Ainshams university; Study Director: Nagwa A Sabry, phD, Ainshams university

Publications and helpful links

General Publications

• ElDash RM, Raslan MA, Shaheen SM, Sabri NA. The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial. F1000Res. 2021 Apr 26;10:321. doi: 10.12688/f1000research.51114.1. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): October 19, 2018
• Study Completion (Actual): October 26, 2018

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: March 27, 2019
• First Posted (Actual): March 29, 2019

Study Record Updates

• Last Update Posted (Actual): April 2, 2019
• Last Update Submitted That Met QC Criteria: April 1, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes; Empagliflozin; Circadian rythm
• 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: EMP-RES-BES-1018/0011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No