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

Study Overview
=================
Brief Summary
-----------------
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

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.

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

Conditions
-----------------
Diabetes Mellitus, Pharmacokinetics, Pharmacodynamics

Intervention / Treatment
-----------------
* Drug: Empagliflozin 10 MG Oral Tablet [Jardiance]


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: A single group of 16 subjects will receive a single oral dose of Empagliflozin 10 MG Oral Tablet [Jardiance] at the morning(Period I) and the same group will receive the same dose of the same drug at the evening(Period II) after a seven days washout period
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Subjects will receive a single oral dose of Empagliflozin 10 MG Oral Tablet [Jardiance] | Drug: Empagliflozin 10 MG Oral Tablet [Jardiance]<br>* Empagliflozin is a sodium-glucose co-transporter 2 inhibitor approved for treatment of type 2 diabetes mellitus<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes, Empagliflozin, Circadian rythm