Serum Pharmacokinetic Disposition and Urinary Excretion of Albendazole

Serum Pharmacokinetic Disposition and Urinary Excretion of Albendazole and Its Metabolites in Non-infected Human Volunteers.

Mass drug administration (MDA) of albendazole (ABZ) to school-age and pre-school-age children is the currently recommended strategy for controlling soil-transmitted helminthiasis (STH) in endemic areas. Recent mathematical modelling suggests that community-wide MDA will be required in order to interrupt transmission of STH. DEWORM3 aims to determine the feasibility of eliminating STH through expanded and intensified MDA strategies. In order to ensure rigorous trial results, it is crucial that the definition of such MDA coverage is informed by unbiased, empirical data. The Centro de Investigación Veterinaria de Tandil (CIVETAN) and Instituto de Investigaciones en Enfermedades Tropicales Universidad Nacional de Salta collaborate on scientific research related to pharmacokinetic studies of ABZ.

This proposal describes the request for funding from DEWORM3 to conduct a study of the serum pharmacokinetic characteristics and urinary excretion of ABZ and its metabolites in non-infected human volunteers to better understand the use of urinary analysis of ABZ as a measure of MDA adherence in the context of DEWORM3.

Study Overview

• Status: Completed
• Conditions: Neglected Tropical Diseases; Soil Transmitted Helminthiasis
• Intervention / Treatment: Drug: Albendazole.

Detailed Description

Objective 1.To characterize the plasma disposition kinetics of ABZ and its main metabolites (ABZ sulphoxide and ABZ sulphone) in non-infected human volunteers.

Objective 2. To characterize the pattern of albendazole (ABZ) and its main metabolites (ABZ sulphoxide and ABZ sulphone) urinary excretion in non-infected human volunteers.

Objective 3. To determine the optimal and the longest period time after treatment where either ABZ and/or its metabolites can be measured in urine as an indirect assessment of an individual's adherence to treatment.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Weight between 45 and 75 Kg.
2. Physical exam without significant abnormal findings.

Exclusion Criteria:

1. Intake of ABZ or other benzimidazole drugs within the last 30 days.
2. Malabsorption or other GI syndromes that could compromise the tolerability or absorption of ABZ.
3. History of hypersensitivity or intolerance to ABZ or its inactive ingredients.
4. Acute clinical conditions.
5. Pregnancy or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Albendazole 400mg p.o. single dose; Volunteers receive 1 tablet albendazole 400mg (GSK) fasting.	Drug: Albendazole.; Single dose 400mg orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Albendazole in urine	Urinary excretion of albendazole (ABZ) and its main metabolites (ABZ sulphoxide and ABZ sulphone) in non-infected human volunteers. PK parameters (Cmax, AUC, Tmax) from levels measured through HPLC	Up to 72 hours

Collaborators and Investigators

• Sponsor: Universidad Nacional de Salta
• Collaborators: CIVETAN CONICET, Facultad de Ciencias Veterinarias, UNCPBA. Tandil
• Investigators: Study Director: Alejandro J Krolewiecki, MD/PhD, Universidad Nacional de Salta

Publications and helpful links

General Publications

• Ceballos L, Krolewiecki A, Juarez M, Moreno L, Schaer F, Alvarez LI, Cimino R, Walson J, Lanusse CE. Assessment of serum pharmacokinetics and urinary excretion of albendazole and its metabolites in human volunteers. PLoS Negl Trop Dis. 2018 Jan 18;12(1):e0005945. doi: 10.1371/journal.pntd.0005945. eCollection 2018 Jan.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2016
• Primary Completion (Actual): December 15, 2016
• Study Completion (Actual): January 20, 2017

Study Registration Dates

• First Submitted: June 16, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (Actual): June 20, 2017

Study Record Updates

• Last Update Posted (Actual): June 22, 2017
• Last Update Submitted That Met QC Criteria: June 20, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Parasitic Diseases; Helminthiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Albendazole
• Other Study ID Numbers: CIVETAN-IIET-ALB01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Publication in peer review journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No