Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04041427 |
| Other study ID # |
ABZ0201 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 17, 2019 |
| Est. completion date |
February 28, 2020 |
Study information
| Verified date |
May 2021 |
| Source |
Universidad Nacional de Salta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This project will develop and assess the feasibility and acceptability of a urine-based assay
to monitor adherence to Mass Drug Administration (MDA) campaigns within Soil-transmitted
helminthiasis (STH) control programs, evaluating the urine and serum pharmacokinetics of
ALBENDAZOLE (ABZ) and its metabolites across a variety of food/fast conditions, age, gender
and body weight. The final goal is to obtain a field ready tool for the measurement of
adherence to anthelmintic treatment at a community level that serves as a coverage/adherence
indicator and a reference standard for other monitoring tools.
Description:
Soil-Transmitted-Helminthic (STH) infections are a major public health issue affecting the
world's poorest populations. Control strategies for STH have been focused on the use of mass
chemotherapy often delivered to school-aged-children; although there is strong interest in
considering community wide MDA to achieve transmission interruption of STH. In these
programs, directly observed treatment is not consistently or frequently achieved and so the
verification of reported adherence is crucial to understanding of the impact of these
programs.
It is important to differentiate a lack of adherence to treatment with albendazole (ABZ) from
absorption/metabolism/resistance-related therapeutic failures. In that context, tools to
evaluate, by means of non-invasive measures, treatment adherence either in adults or
children, should be developed. In addition, drug absorption and metabolism among people may
vary enormously depending on different factors such as genetics, age, gender, diet, weight
and disease. Any of those factors may alter the ABZ/metabolites disposition kinetics and,
consequently, the exposure of the target STH to the active drug.
The current research project proposes to establish evidence for the feasibility and usability
of such a tool within MDA programs from the perspectives of the end-user (community),
implementing partners, National Neglected Tropical Diseases (NTD) program and the World
Health Organization. The proposed use case for this currently developed assay is to confirm
the findings of the standard coverage survey (based on self-report) in the context of
community MDA. Further validation and technical development of a field ready tool for
monitoring adherence to albendazole, in addition to the identification of key factors
affecting drug therapeutic response is proposed within this project.
Main goals of the current proposal:
1. To assess key factors affecting the feasibility of using a urinary assay to monitor
adherence to MDA within STH control programs, including tool acceptability, tool
learnability, system capacity to deliver, timing of administration, frequency of
administration, adequate breadth of administration, sustainability of use,
responsiveness of health systems to tool output, and efficiency of administration.
2. To evaluate the influence of diet, fasting, age, gender and body weight on the serum
disposition kinetics and pattern of urinary excretion of ABZ/metabolites in non-infected
human volunteers.
3. To evaluate the relationship between drug serum/urine concentrations with potential
factors affecting ABZ/metabolites disposition kinetics in children.
4. To characterize the pattern of amino-ABZSO2 urinary excretion in non-infected human
volunteers treated with ABZ and to determine the longest period of time after ABZ
treatment where amino-ABZSO2 can be measured in urine (alternatively to ABZSO) as an
indirect assessment of an individual's adherence to treatment.
5. To determine drug/metabolites chemical stability in urine samples at different
temperatures (reproducing environmental conditions of tropical weather).
Study procedures:
Twelve (12) healthy adult volunteers (body weight between 45 and 75 kg, women n=6 and men
n=6) will participate in a crossover design with three (3) different experimental phases. In
Phase I, volunteers will be assigned to either Group I, Group II or Group III (n=4 each, two
female and two male individuals). In the following 2 Phases of the study, volunteers will be
cross-over between the other 2 Groups, with a 14-day washout period between Phases. All
groups and phases will receive 400 mg of ABZ (Glaxo SmithKline).
Group I (heavy meal):30 minutes after a high-fatty meal (estimated fat content 40 g).
Group II (light meal):30 minutes after a light meal (infusion tea). Group III (fasted):at
8-hours fasting condition.
Prior to ABZ treatment (sampling time =0), a baseline blood (5 mL) and urine (10 mL) samples
will be obtained in each phase. Venous blood samples will be collected at 2, 4, 8, 12, 24,
36, 48 and 72 h, after ABZ administration. Urine samples will be collected at 2, 4, 8, 12,
24, 36, 48 and 72 h post-treatment. Samples will be stored at -20ºC until HPLC analysis of
ABZ/metabolites.
Urine samples from time 4-hours will be aliquoted in 3 in order to evaluate the effect of
storage at 32°C (in an incubator) for 12 and 24 hours before freezing at -20°C in the
measurement of drug/metabolite levels. A total of 12 samples from Group 1 will be included in
this sub-sample analysis which will provide information on the stability of the samples at
temperatures in tropical environments.
