Clinical trial NCT03895229: The Effect of Morning Versus Evening Administration on The Pharmacokinetics and Pharmacodynamics of Empagliflozin
Official title: The Effect of Morning Versus Evening Administration on The Pharmacokinetics and Pharmacodynamics of Empagliflozin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus
Pharmacokinetics
Pharmacodynamics
Keywords: Diabetes
Empagliflozin
Circadian rythm
Lead sponsor: Ain Shams University
Sponsor class: OTHER
Collaborators: name: Drug Research Centre, Cairo, Egypt
First posted: 2019-03-29
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Maximum drug concentration in plasma (Cmax)
timeFrame: 0 up to 4 hours
measure: Area under the plasma concentration-time curve from time 0 to 48 hours(h) (AUC0→48h)
timeFrame: From first sampling interval up to 48 hours
measure: Time to Maximum drug concentration in plasma (tmax)
timeFrame: 0 up to 4 hours
Secondary outcomes:
measure: Cumulative Urinary Glucose Excreted over the first 24 hours (Cumulative UGE)
timeFrame: From 0 up to 24 hours
measure: Half life( t½) of drug in plasma
timeFrame: Up to 48 hours
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Drug research centre
Study officials:
affiliation: Ainshams University
name: Rana M Ali, MD student
role: PRINCIPAL_INVESTIGATOR
affiliation: Ainshams University
name: Nagwa A Sabry, phD
role: STUDY_DIRECTOR
References:
citation: 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.