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

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.

• Mebendazole (Drug): 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 (Drug): 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.

Primary outcomes

• Cure Rate for Ascaris Lumbricoides at the End of Double-blind Treatment Period [At Visit 3 (Day 19) 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.
• Cure Rate for Trichuris Trichiura at the End of Double-blind Treatment Period [At Visit 3 (Day 19) 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.
• Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Double-Blind Treatment Period [Up to Visit 3 (Day 19 +/-2)]: 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.
• Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Open-Label Treatment Period [At Visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3)]: 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.

Secondary outcomes

• Egg Count Reduction Rate (Percent) for Ascaris Lumbricoides Infestation at the End of Double-blind Treatment Period [Baseline and Day 19 (Visit 3) 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.
• Egg Count Reduction Rate (Percent) for Trichuris Trichiura Infestation at the End of Double-blind Treatment Period [Baseline and Day 19 (Visit 3) 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.
• Maximum Plasma Concentration (Cmax) of Mebendazole [Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)]: The Cmax is the maximum plasma concentration.
• Time to Reach Maximum Plasma Concentration (Tmax) of Mebendazole [Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)]: The Time to Reach Maximum Plasma Concentration (Tmax) is time to reach the maximum plasma concentration.
• Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours (AUC8h) of Mebendazole [Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)]: The (AUC8h) is the area under the plasma concentration-time curve from time 0 to 8 hours Post-dose.
• Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) of Mebendazole [Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)]: The (AUC \[0-last\]) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.

Sex: All, ages: 1 Year to 16 Years

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

Participant flow

Outcome results

• Cure Rate for Ascaris Lumbricoides at the End of Double-blind Treatment Period (Primary), Number, percentage of participants: Double-blind Placebo 11.1 (5.2 to 20.1); Double-blind Mebendazole 500 mg 83.7 (74.2 to 90.8) (p < 0.001)
• Cure Rate for Trichuris Trichiura at the End of Double-blind Treatment Period (Primary), Number, percentage of participants: Double-blind Placebo 7.6 (3.5 to 13.9); Double-blind Mebendazole 500 mg 33.9 (25.6 to 42.9) (p < 0.001)
• Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Double-Blind Treatment Period (Primary), Number, participants: Double-blind Placebo 8; Double-blind Mebendazole 500 mg 9
• Egg Count Reduction Rate (Percent) for Ascaris Lumbricoides Infestation at the End of Double-blind Treatment Period (Secondary), Number, percent change in egg count: Double-blind Placebo -19.2 +/- 20684.03; Double-blind Mebendazole 500 mg -97.9 +/- 23476.82 (p < 0.001)
• Egg Count Reduction Rate (Percent) for Trichuris Trichiura Infestation at the End of Double-blind Treatment Period (Secondary), Number, percent change in egg count: Double-blind Placebo -10.5 +/- 930.05; Double-blind Mebendazole 500 mg -59.7 +/- 1256.22 (p < 0.001)
• Maximum Plasma Concentration (Cmax) of Mebendazole (Secondary), Mean, nanogram per Milliliters (ng/mL): Mebendazole: Group 1 (1 to <3 Years) 210.0 +/- 212.0; Mebendazole: Group 2 (3 to 6 Years) 49.9 +/- 26.8; Mebendazole: Group 3 (7 to 16 Years) 34.2 +/- 13.8
• Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Open-Label Treatment Period (Primary), Number, participants: Open-label Mebendazole 500 mg 7
• Time to Reach Maximum Plasma Concentration (Tmax) of Mebendazole (Secondary), Mean, hours: Mebendazole: Group 1 (1 to <3 Years) 2.5 (1 to 8); Mebendazole: Group 2 (3 to 6 Years) 2 (0.98 to 3); Mebendazole: Group 3 (7 to 16 Years) 3 (1 to 8)
• Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours (AUC8h) of Mebendazole (Secondary), Mean, nanogram hour per Milliliters(ng*h/mL): Mebendazole: Group 1 (1 to <3 Years) 697 +/- 367; Mebendazole: Group 2 (3 to 6 Years) 242 +/- 139; Mebendazole: Group 3 (7 to 16 Years) 182 +/- 66.3
• Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) of Mebendazole (Secondary), Mean, ng*h/mL: Mebendazole: Group 1 (1 to <3 Years) 1320 +/- 844; Mebendazole: Group 2 (3 to 6 Years) 416 +/- 215; Mebendazole: Group 3 (7 to 16 Years) 387 +/- 190

Adverse events

Time frame: Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])

Other adverse events by term

• Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC