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Trial record 6 of 9 for:    "Trichuriasis" | "Antiparasitic Agents"

Albendazole Dose Finding and Pharmacokinetics in Children and Adults

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ClinicalTrials.gov Identifier: NCT03527745
Recruitment Status : Active, not recruiting
First Posted : May 17, 2018
Last Update Posted : September 23, 2019
Sponsor:
Collaborator:
Centre Suisse de Recherches Scientifiques (CSRS)
Information provided by (Responsible Party):
Jennifer Keiser, Swiss Tropical & Public Health Institute

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Trichuriasis Hookworm Infections Drug: Albendazole Drug: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1040 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 23, 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Albendazole

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 Name: 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 (400mg, dependent on treatment cohort)
Other Name: 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 (600mg, dependent on treatment cohort)
Other Name: 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 (800mg, dependent on treatment cohort)
Other Name: 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.




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. Egg-reduction rate (ERR) against T. trichiura and hookworm infections [ Time Frame: 14-21 days after treatment ]
    Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment to assess the corresponding ERRs.

  2. Maximum concentration (Cmax) of albendazole and its metabolites [ 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 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.

  3. Time to reach Cmax (tmax) of albendazole and its metabolites [ 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 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.

  4. Area under the curve (AUC) of albendazole and its metabolites [ Time Frame: 0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing ]
    To determine the area under the curve (AUC) of albendazole and its metabolites 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03527745


Locations
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Côte D'Ivoire
Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)
Abidjan, Côte D'Ivoire
Sponsors and Collaborators
Jennifer Keiser
Centre Suisse de Recherches Scientifiques (CSRS)

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Responsible Party: Jennifer Keiser, Prof. Jennifer Keiser, PhD, Swiss Tropical & Public Health Institute
ClinicalTrials.gov Identifier: NCT03527745     History of Changes
Other Study ID Numbers: 2
First Posted: May 17, 2018    Key Record Dates
Last Update Posted: September 23, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Trichuriasis
Antiparasitic Agents
Hookworm Infections
Ancylostomiasis
Strongylida Infections
Secernentea Infections
Nematode Infections
Helminthiasis
Parasitic Diseases
Enoplida Infections
Adenophorea Infections
Albendazole
Anthelmintics
Anti-Infective Agents
Anticestodal Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents