Clinical trial NCT05589688: Individualization of Dosage Regimens in Obese Patients: Application to Acyclovir
Official title: Individualization of Dosage Regimens in Obese Patients: Application to Acyclovir
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Obesity
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2022-10-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Renal elimination clearance
timeFrame: Day 1
Secondary outcomes:
measure: the interindividual variability of acyclovir exposure : lean mass
timeFrame: Day 1
measure: the interindividual variability of acyclovir exposure : glomerular filtration rate
timeFrame: Day 1
measure: the qualitative compilation of adverse events associated with acyclovir infusion observed and reported by the volunteer.
timeFrame: Day 1, Day 2
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Toulouse Hospital
Study officials:
affiliation: University Hospital, Toulouse
name: Sarah Baklouti, PharmD
role: PRINCIPAL_INVESTIGATOR
References: