A Study to Assess the Efficacy and Safety of Mebendazole for the Treatment of Helminth Infections in Pediatric Participants

A Double-Blind, Randomized, Multi-Center, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Single Dose of a 500-mg Chewable Tablet of Mebendazole in the Treatment of Soil-Transmitted Helminth Infections (Ascaris Lumbricoides and Trichuris Trichiura) in Pediatric Subjects

The purpose of this study is to evaluate the efficacy and safety of mebendazole compared with placebo in pediatric participants with Helminth infections.

Study Overview

• Status: Completed
• Conditions: Helminth Infections
• Intervention / Treatment: Drug: Mebendazole; Drug: Placebo

Detailed Description

This will be a double-blind (neither physician nor participant knows the treatment that the participant receives), randomized (the study drug is assigned by chance), multi-center, parallel-group study (each group of participants will be treated at the same time) to evaluate the efficacy and safety of mebendazole (a drug currently being investigated for Helminth gastrointestinal infections) compared with placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) in children (including pre-school and school-aged children) with Helminth infections. The study will consist of 3 phases: a screening phase, a double-blind treatment phase, and a post-treatment (or follow-up) phase. A pharmacokinetic (explores what a drug does to the body) open-label substudy (asks a separate research question from the parent study while using the same participant population but does not contribute to the parent study's objectives) will be included in the parent study to measure the level of mebendazole in the blood. Safety assessments will be performed throughout the study. Each participant will take part in the study for approximately 30 days.

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 3

Contacts and Locations

Study Locations

• Ethiopia
  • Gondar, Ethiopia
  • Jimma, Ethiopia
• Rwanda
  • Kigali, Rwanda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female participants who are >=9 years old must have a negative urine pregnancy test at screening or at the time of randomization
• Participants must be an otherwise healthy child, based on medical history, physical examination, vital signs, hemoglobin, and concomitant medications
• Participants >=3 years of age must have teeth and be able to chew
• Participant must be available to return to the study site for all visits, including the follow-up visit
• Parent(s)/guardians of participants (or their legally-accepted representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to have their child participate in the study
• Children 6 years of age and older will be asked to assent (agree) to their participation using appropriate language to their level of understanding; assent will be documented

Exclusion Criteria:

• Participant has active diarrhea (defined as the passage of 3 or more loose or liquid stools per day) at screening or at the time of randomization
• Participant has a significant medical disorder, participant has difficulty in chewing or swallowing
• Participant has significant anemia (<8 g/dL)
• Participant has significant wasting (greater than 2 standard deviations below the mean World Health Organization [WHO] Child Growth Standards for weight-for-height or body mass index)
• Participant has a known hypersensitivity to mebendazole, any inert ingredients in the chewable formulation
• Participant has preplanned surgery/procedures that would interfere with the conduct of the study during the course of study
• Participants has received an investigational drug (including vaccines) or used an investigational medical device within 30 days before the planned start of treatment, or is currently enrolled in an investigational study
• Employees of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator
• Participant has taken any form of medication containing mebendazole or any other treatment for soil transmitted helminth infection within 30 days of entry into the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Mebendazole; Mebendazole will be administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) and in an open-label manner at Visit 4 (Day 21).	Drug: Mebendazole; Mebendazole will be administered as a single-dose 500 mg chewable tablet. For children 1 year to <36 months of age, the tablet will be placed in a teaspoon and bottled water will be poured into the remaining volume of the teaspoon. The tablet will then be allowed to absorb all water (absorption time has been observed to take less than 1 minute) to become a soft semi-solid mass without any hard particles. This semi-solid form can then be easily ingested by the child.
Placebo Comparator: Placebo; Matching placebo will be administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1).	Drug: Placebo; Matching placebo will be administered as a single-dose chewable tablet. For children 1 year to <36 months of age, the tablet will be placed in a teaspoon and bottled water will be poured into the remaining volume of the teaspoon. The tablet will then be allowed to absorb all water (absorption time has been observed to take less than 1 minute) to become a soft semi-solid mass without any hard particles. This semi-solid form can then be easily ingested by the child.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure Rate for Ascaris Lumbricoides at the End of Double-blind Treatment Period	Cure is defined as a post-treatment egg count of zero in participants who had a positive egg count at baseline.	At Visit 3 (Day 19) of Double-blind treatment period
Cure Rate for Trichuris Trichiura at the End of Double-blind Treatment Period	Cure is defined as a post-treatment egg count of zero in participants who had a positive egg count at baseline.	At Visit 3 (Day 19) of Double-blind treatment period
Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Double-Blind Treatment Period	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Up to Visit 3 (Day 19 +/-2)
Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Open-Label Treatment Period	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	At Visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Egg Count Reduction Rate (Percent) for Ascaris Lumbricoides Infestation at the End of Double-blind Treatment Period	Percent egg count reduction is calculated as average egg count at end of treatment period of a treatment group minus average egg count at baseline of the treatment group divided by average egg count at baseline of the treatment group.	Baseline and Day 19 (Visit 3) at the End of Double-blind Treatment Period
Egg Count Reduction Rate (Percent) for Trichuris Trichiura Infestation at the End of Double-blind Treatment Period	Percent egg count reduction is calculated as average egg count at end of treatment period of a treatment group minus average egg count at baseline of the treatment group divided by average egg count at baseline of the treatment group.	Baseline and Day 19 (Visit 3) at the End of Double-blind Treatment Period
Maximum Plasma Concentration (Cmax) of Mebendazole	The Cmax is the maximum plasma concentration.	Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)
Time to Reach Maximum Plasma Concentration (Tmax) of Mebendazole	The Time to Reach Maximum Plasma Concentration (Tmax) is time to reach the maximum plasma concentration.	Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)
Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours (AUC8h) of Mebendazole	The (AUC8h) is the area under the plasma concentration-time curve from time 0 to 8 hours Post-dose.	Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) of Mebendazole	The (AUC [0-last]) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.	Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 9, 2014
• First Submitted That Met QC Criteria: January 9, 2014
• First Posted (Estimate): January 13, 2014

Study Record Updates

• Last Update Posted (Estimate): November 4, 2016
• Last Update Submitted That Met QC Criteria: September 16, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Pediatric; Mebendazole; Placebo; Helminths; School aged; Helminth infections; Preschool aged; Vermox
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Parasitic Diseases; Infections; Communicable Diseases; Helminthiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Mebendazole; Piperazine; Piperazine citrate; DMP 777
• Other Study ID Numbers: CR100933; MEBENDAZOLGAI3003 (Other Identifier: Janssen Research & Development, LLC)