Individualization of Dosage Regimens in Obese Patients: Application to Acyclovir (ACICLOPTIM)

The number of obese people will reach 50% of the world population by 2035. Obesity is a chronic disease. For obese patients, dosage regimens have been determined for patients with a "normal" BMI between 20-30 kg/m2. Based on plasma and urine concentrations, a pharmacokinetic model will be performed to study in healthy volunteers, the predictive character of lean mass, measured by DEXA, on renal elimination and therefore on acyclovir exposure. The main objective of this study is to evaluate, in 4 volunteers groups representative of (1) non-obese (18-24.9 kg/m2), (2) overweight (25-29.9 kg/m2), (3) grade 1 obesity (30-34.9 kg/m2) and (4) grade 2 obesity (35-39.9 kg/m2), the predictive nature of lean mass, measured by DEXA, on renal elimination and therefore on acyclovir exposure.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Acyclovir

Detailed Description

This study will complement the clinical data on acyclovir in healthy volunteers considering that current knowledge in terms of drugs use in obese subjects is not sufficient to guarantee the efficacy and/or toxicity absence of exposure. As a consequence, this lack of certainties leads physicians to propose dosages without exceeding a threshold defined according to (i) their experience, (ii) data obtained for BMI < 30 kg/m2 and/or (iii) an approximate criterion derived from the total weight (adjusted weight...). Acyclovir is a systemic antiviral drug indicated for the treatment of Herpes Simplex virus (HSV) and Varicella Zoster (VZV) mucosal infections at 15 mg/kg/d in three divided doses, or more severe infections (e.g., herpetic meningoencephalitis) at higher dosage regimen (30 to 45 mg/kg/d in three divided doses).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sarah Baklouti, PharmD; Phone Number: 05 67 69 03 83; Email: baklouti.s@chu-toulouse.fr
• Study Contact Backup: Name: Charline DAGUZAN; Phone Number: 05 61 77 84 90; Email: daguzan.c@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• healthy volunteers with a BMI between 18 and 39,9 kg/m2, divided into 4 groups: 5 non-obese volunteers (BMI between 18 and 24,9 kg/m2), 5 overweight volunteers (BMI between 25 and 29,9 kg/m2), 5 volunteers with grade 1 obesity (BMI between 30 and 34,9 kg/m2) and 5 volunteers with grade 2 obesity (BMI between 35 and 39,9 kg/m2),
• volunteers with a aGFR > 50 ml/min,
• with a good venous pathway for kinetics,
• women on contraception or postmenopausal women,
• person who has given written consent and affiliated with the public health insurance.

Exclusion Criteria:

• volunteers with nephrotoxic co-prescriptions and/or co-prescriptions that would modify the pharmacokinetics of acyclovir like diuretics, NSAIDs or statins,
• having presented serious allergies to a drug (e.g. angioedema...), with large parenchyma insufficiencies (e.g., hepatic insufficiency, heart failure...),
• with diabetes or taking anti-diabetics due to the possible deterioration of renal function in diabetic patients,
• with arterial hypertension or taking antihypertensive drugs due to the possible modification of renal clearance by modification of blood flow,
• drug interactions with acyclovir (H2 receptor antagonists (e.g., Cimetidine), Probenecid, Mycophenolate Mofetil, Lithium, Anti-calcineurins (Ciclosporin, Tacrolimus)),
• volunteers taking anticoagulants,
• hypersensitivity to acyclovir,
• pregnant woman,
• participation in another clinical study in the last two months
• volunteers with ongoing viral HSV/VZV infection treated with acyclovir,
• adults under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: acyclovir; Subjects take a single dose of 5 mg/kg infused over 1 hour.	Drug: Acyclovir; Subjects will receive a single dose of 5 mg/kg infused over 1 hour. Then, 13 blood samples after placement of a catheter, and 4 urine samples will be taken over the 12 hours following the start of administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal elimination clearance	To quantify the relationship between lean body mass, measured by Dual-energy x-ray absorptiometry (DEXA), and the true absolute glomerular filtration rate (GFRa) which is estimated by the renal elimination clearance of acyclovir.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the interindividual variability of acyclovir exposure : lean mass	To measure lean mass by DEXA on subjects	Day 1
the interindividual variability of acyclovir exposure : glomerular filtration rate	A blood sample will be taken for this purpose to assess the renal function of the volunteer by measuring his uremia and his creatinine allowing the calculation of the glomerular filtration rate.	Day 1
the qualitative compilation of adverse events associated with acyclovir infusion observed and reported by the volunteer.	adverse events reported by volunteers	Day 1, Day 2

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Sarah Baklouti, PharmD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 21, 2022

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Acyclovir
• Other Study ID Numbers: RC31/21/0610

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