Albendazole Dose Finding and Pharmacokinetics in Children and Adults

May 11, 2023 updated by: Jennifer Keiser

Efficacy and Safety of Ascending Dosages of Albendazole Against T. Trichiura and Hookworm in Preschool- and School-aged Children and Adults: a Randomized Controlled Trial

This study is a single-blind randomized clinical trial conducted in rural Côte d'Ivoire. This study aims at providing evidence on the dose-response of increasing oral albendazole dosages against whipworm (T. trichiura) and hookworm infections in preschoolers (2-5 years), school-aged children (6-12 years) and adults (≥ 21 years).

The primary objective is to determine cure rates (primary end point, i.e. conversion from being egg positive pre-treatment to egg negative post-treatment). Secondary objectives involve the determination of egg reduction rates (the reduction in the number of excreted eggs from baseline (prior to treatment) to follow-up) and the assessment of safety of ascending dosages of albendazole (secondary end points). In addition, key pharmacokinetic parameters will be determined from blood samples collected with a micro-sampling device (secondary end point).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a single-blind randomized clinical trial conducted in Côte d'Ivoire. This study aims at providing evidence on the efficacy and safety of ascending oral albendazole dosages in children and adults infected with T. trichiura and hookworm. In preschool-aged children (2-5 years) (i) 200 mg, (ii) 400 mg and (iii) 600 mg; in schoolchildren (6-12 years) and adults (≥ 21 years) (i) 200 mg (only for hookworm infections), (ii) 400 mg, (iii) 600 mg and (iv) 800 mg will be administered and efficacy, safety and pharmacokinetic parameters will be assessed.

The primary objective is to determine the dose-response based on cure rates of albendazole in preschool-aged children (2-5 years), school-aged children (6-12 years) and adults (≥ 21 years) infected with T. trichiura and hookworm.

The secondary objectives of the trial are to determine the efficacy based on egg reduction rates of albendazole in preschool-aged children, school-aged children and adults, to determine an exposure (including length of time that the drug concentration is above the MIC, Cmax, AUC)-response correlation of albendazole in preschool-aged children, school-aged children and adults, to evaluate the safety and tolerability of albendazole in preschool-aged children, school-aged children and adults, and to determine the efficacy against concomitant soil-transmitted helminthiasis (Ascaris lumbricoides).

After obtaining informed consent from individual/parents and/or caregiver, the medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical examination and venipuncture to examine biochemical parameters in the blood carried out by the study physician before treatment. Enrollment will be based on two stool samples that will be collected, if possible, on two consecutive days or otherwise within a maximum of 5 days.

All stool samples will be examined with duplicated Kato-Katz thick smears by experienced laboratory technicians. Randomization of participants into the treatment arms will be stratified according to intensity of infection. All participants will be interviewed before treatment, 3 and 24 hours and 3 weeks after treatment about the occurrence of adverse events. Children and adults will be sampled using finger pricking for micro-blood sampling at 0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing.

The primary analysis will include all participants with primary end point data (available case analysis). Supplementary, a per-protocol analysis and an intention-to-treat analysis will be conducted. CRs will be calculated as the percentage of egg-positive subjects at baseline who become egg-negative after treatment. Differences among CRs will be analysed by using crude logistic regressions and adjusted logistic regressions (adjustment for age, sex, and height).

Geometric and arithmetic mean egg counts will be calculated for the different treatment arms before and after treatment to assess the corresponding ERRs. Bootstrap resampling method with 2,000 replicates will be used to calculate 95% confidence intervals (CIs) for differences in ERRs. Noncompartmental and nonlinear mixed-effects (NLME) modeling will be used to determine PK parameters.

Study Type

Interventional

Enrollment (Actual)

700

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Côte D'Ivoire
      • Abidjan, Côte D'Ivoire
        • Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male and female adults (≥21 years), preschool-aged children (2-5 years) and school-aged children (6-12 years) infected with T. trichiura/hookworm
  2. Written informed consent/assent signed from parent/guardian
  3. Positive for T. trichiura/hookworm by at least two slides of the quadruple Kato-Katz thick smears and infection intensities of at least 100 eggs per gram of stool (EPG)
  4. Agree to comply with study procedures, including provision of two stool samples at the beginning (baseline) and approximately three weeks after treatment (follow-up).

Exclusion Criteria:

  1. Presence of acute or uncontrolled systemic illnesses (e.g. severe anemia, infection, clinical malaria) as assessed by a medical doctor, upon initial clinical assessment and liver function tests.
  2. Known or reported history of chronic illness such as HIV, acute or chronic hepatitis, cancer, diabetes, chronic heart disease or renal disease.
  3. Prior treatment with anthelmintics (eg, diethylcarbamazine [DEC], suramin, ivermectin, mebendazole or albendazole) within 4 weeks before planned test article administration.
  4. Received any investigational drugs or investigational devices within 4 weeks before administration of test article that may confound safety and/or efficacy assessments.
  5. Known or suspected allergy to benzimidazoles.
  6. Pregnant (urine testing) or breastfeeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 200 mg albendazole
against T. trichiura in preschool-aged children or against hookworm infections in preschool-aged children, school-aged children and adults
Drug: Albendazole
Single dose of albendazole (200mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (400mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (600mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (800mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Experimental: 400 mg albendazole
against T. trichiura in preschool-aged children, school-aged children and adults or against hookworm infections in preschool-aged children, school-aged children and adults
Drug: Albendazole
Single dose of albendazole (200mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (400mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (600mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (800mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Experimental: 600 mg albendazole
against T. trichiura in preschool-aged children, school-aged children and adults or hookworm infections in preschool-aged children, school-aged children and adults
Drug: Albendazole
Single dose of albendazole (200mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (400mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (600mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (800mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Experimental: 800 mg albendazole
against T. trichiura in school-aged children and adults or against hookworm infections in school-aged children and adults
Drug: Albendazole
Single dose of albendazole (200mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (400mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (600mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Drug: Albendazole
Single dose of albendazole (800mg, dependent on treatment cohort)
Other Names:
  • Zentel®
Placebo Comparator: Placebo
against T. trichiura in preschool-aged children, school-aged children and adults or hookworm infections in preschool-aged children, school-aged children and adults
Drug: Placebo
Matching placebo tablets will be obtained from Fagron, Germany.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cure Rate Against T. Trichiura and Hookworm Infections
Time Frame: 14-21 days after treatment
The conversion from being egg positive pre-treatment to egg negative post-treatment, or cure rate (CR).
14-21 days after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Egg-reduction Rate (ERR) Against T. Trichiura and Hookworm Infections, Respectively
Time Frame: 14-21 days after treatment
Percent change in geometric mean eggs per gram of stool from before to after treatment
14-21 days after treatment
Maximum Concentration (Cmax) of Albendazole Sulphoxide
Time Frame: 0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing
To determine maximum drug concentration (Cmax) of albendazole and its metabolites in adults (≥ 21 years), preschool-aged (2-5 years) and school-aged children (6-12 years). Albendazole sulfoxide will be quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Drug concentrations will be calculated by interpolation from a calibration curve with a foreseen limit of quantification of approximately 1-5 ng/ml.
0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing
Time to Reach Cmax (Tmax) of Albendazole Sulphoxide
Time Frame: 0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing
To determine time to reach Cmax (tmax) of albendazole and its metabolites in adults (≥ 21 years), preschool-aged (2-5 years) and school-aged children (6-12 years). Albendazole sulfoxide was quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Drug concentrations will be calculated by interpolation from a calibration curve with a foreseen limit of quantification of approximately 1-5 ng/ml.
0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing
Area Under the Curve (AUC) of Albendazole Sulphoxide
Time Frame: 0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing
To determine the area under the curve (AUC) of albendazole sulphoxide in adults (≥ 21 years), preschool-aged (2-5 years) and school-aged children (6-12 years). Albendazole and its metabolites (albendazole sulfoxide and albendazole sulfone) will be quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Drug concentrations will be calculated by interpolation from a calibration curve with a foreseen limit of quantification of approximately 1-5 ng/ml.
0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jennifer Keiser

Collaborators

Centre Suisse de Recherches Scientifiques en Cote d'Ivoire

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2018

Primary Completion (Actual)

April 17, 2019

Study Completion (Actual)

April 17, 2019

Study Registration Dates

First Submitted

May 3, 2018

First Submitted That Met QC Criteria

May 16, 2018

First Posted (Actual)

May 17, 2018

Study Record Updates

Last Update Posted (Actual)

June 12, 2023

Last Update Submitted That Met QC Criteria

May 11, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2 (Other Identifier: Instituto Cardiovascular de Buenos Aires)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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