Pharmacokinetics of Dexamethasone in COVID-19 Obese Patients (CoDEX)

In this regard, the present research project aims to compare dexamethasone PK in normal-weight versus obese patients treated for COVID-19.

This observational study will include patients hospitalized at HUG (Division of General Internal Medicine) with COVID-19 and treated with oral DEX. This study will include 2 groups of patients according to their body mass index (BMI) (normal weight with a BMI of 18.5-25.0 kg/m2; obese/ morbidly obese with a BMI ≥30). The primary outcome will be the assessment of the differential impact of weight on DEX PK. Finally, the data generated will be used to build a physiologically based PK (PBPK) model for DEX and in different sub-groups. The model will aim to predict the effect of BMI in virtual populations with different drugs and in different scenarios. This should allow prospective dose adjustment of DEX based on patient weight.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Capillary blood sampling

Detailed Description

Before starting the study, COVID-19 patients receiving dexamethasone as part of their hospital management and meeting the criteria of inclusion and non-exclusion will have an information session with an investigator as described above.

During the study session, capillary blood samples will be taken during a total of 8 hours, time starting just before DEX administration, and at the following times after the dose: time of the drug intake, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours. The capillary blood sample will be obtained by pricking the fingertip using contact-activated lancet (BD Microtainer). A total of five blood drops (10 μL each) will be collected by a micropipette and will be dropped off on the blotting paper 903 S&S (Whatman). After a 45-minute drying time at room temperature, dried blood samples (DBS) samples will be packed in sealable plastic bags containing a desiccant and stored at - 80°C until analysis. Drugs will be extracted from DBS using methanol. DEX quantification in capillary DBS will be performed using reverse-phase- HPLC coupled to tandem mass spectrometer (MS/MS). In addition to this, an EDTA tube (3 ml) of blood will be collected and preserved in the biobank (-80°C) and will be used whether further analysis should be performed on the samples. In this aim an authorization to reuse the samples will be requested from each patient during the consent signature.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • University Hospitals of Geneva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Thirty COVID-19 hospitalized patients will be informed and included in the study after giving a written informed consent. The control group will include mainly normal weight patients (BMI 18.5- 25 kg/m2) receiving DEX.

Description

Inclusion Criteria:

• Male and female patients ≥ 18 years receiving DEX for COVID-19
• Stable dose of DEX for at least 24 hours
• BMI between 18.5 and 25 or ≥ 30 kg/m2
• Understanding of French orEnglish languages and ability to give a written inform consent

Exclusion Criteria:

• Medical history of cirrhosis (Child Pugh B and C) or/and nonalcoholic fatty liver disease.
• History of bariatric or other gastric surgery that may affect the drug absorption
• Patient already included in a clinical trial of an investigational drug
• Use of drugs that may affect CYP3A activity * *based on the 'drug interactions and cytochromes P450' table published by The Division of clinical Pharmacology and Toxicology [15], HUG and on the investigator's knowledge and on the drug interactions website from the University of Liverpool (https://www.covid19- druginteractions.org/checker).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal weight; The patients (n=30) will be stratified into 2 groups based on their body mass Index (BMI).The normal weight group will contain 15 patients with a 18.5 ≤ BMI ≤ 25 kg/m2. Each group will be divided in two subgroups (female/ male)	Other: Capillary blood sampling; The capillary blood sample will be obtained by pricking the fingertip using contact-activated lancet (BD Microtainer). A total of five blood drops (10 μL each) will be collected by a micropipette and will be dropped off on the blotting paper 903 S&S (Whatman).
Obese; The patients (n=30) will be stratified into 2 groups based on their body mass Index (BMI). The obese group will contain 15 patients with a BMI ≥ 30 kg/m2. Each group will be divided in two subgroups (female/ male)	Other: Capillary blood sampling; The capillary blood sample will be obtained by pricking the fingertip using contact-activated lancet (BD Microtainer). A total of five blood drops (10 μL each) will be collected by a micropipette and will be dropped off on the blotting paper 903 S&S (Whatman).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC comparison	The primary endpoint will be the AUC of DEX determined after a 6 mg oral dose at steady state.	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters	Extrapolation from the AUC values of the Dexamethasone Clearance in the two groups	8 hours
PK parameters	Extrapolation from the AUC values of the Dexamethasone Cmax in the two groups	8 hours
PK parameters	Extrapolation from the AUC values of the Dexamethasone T1/2 in the two groups	8 hours

Collaborators and Investigators

• Sponsor: Jules Desmeules

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 2, 2021
• Primary Completion (ACTUAL): February 9, 2021
• Study Completion (ACTUAL): April 16, 2021

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (ACTUAL): August 9, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2021
• Last Update Submitted That Met QC Criteria: August 6, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Dexamethasone
• Other Study ID Numbers: 2021-00034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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