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

Toulouse University Hospital

Status and phase

Enrolling

Phase 1

Conditions

Obesity

Treatments

Drug: Acyclovir

Study type

Interventional

Funder types

Other

Identifiers

NCT05589688

RC31/21/0610

Details and patient eligibility

About

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.

Full 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).

Enrollment

20 estimated patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

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