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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02034162
• Collaborator: (none)
• Enrollment: 295
• Locations: 3
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 98.3
• Patients Per Site Per Month: 10.9

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Helminth Infections	Drug: Mebendazole; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 295 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Gondar		Ethiopia
2		Jimma		Ethiopia
3		Kigali		Rwanda

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02034162
• Other Study ID Numbers: CR100933; MEBENDAZOLGAI3003
• First Posted: Jan 13, 2014
• Last Update Posted: Nov 4, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Janssen Research & Development, LLC: Helminth infections; Helminths; Pediatric; Preschool aged; School aged; Mebendazole; Vermox; Placebo
• Additional relevant MeSH terms: Infections; Communicable Diseases; Helminthiasis; Mebendazole; Piperazine; Piperazine citrate; DMP 777

Study Results

Participant Flow

Recruitment Details	The study was conducted from 8-Dec-2014 to 3-Sep-2015. A total of 295 participants were enrolled and randomly assigned to study treatment; 278 participants completed the study. Of the 295 participants, 167 participants were reported with Ascaris lumbricoides infestation and 243 participants were reported with Trichuris trichiura infestation.
Pre-assignment Detail	Of the 792 participants screened, a total of 295 were randomly assigned to study treatments, of which 278 completed the study. 17 participants were withdrawn from study with following reasons: Withdrawal by participant (12), Lost to follow-up (3), Physician decision (1) and Protocol violation (1).

Arm/Group Title	Double-blind Placebo	Double-blind Mebendazole 500 mg	Open-label Mebendazole 500 mg
Arm/Group Description	Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole 500-mg chewable tablet was administered in an open label manner at visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3).
Period Title: Double-blind
STARTED	146	149	0
COMPLETED	137	141	0
NOT COMPLETED	9	8	0
Period Title: Double-blind
STARTED	0	0	278
COMPLETED	0	0	278
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Double-blind Placebo	Double-blind Mebendazole 500 mg	Total
Arm/Group Description	Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Total of all reporting groups
Overall Participants	146	149	295
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.7 (3.09)	7.9 (3.27)	7.8 (3.18)
Sex: Female, Male (Count of Participants)
Female	74 50.7%	78 52.3%	152 51.5%
Male	72 49.3%	71 47.7%	143 48.5%
Region of Enrollment (participants) [Number]
ETHIOPIA	127 87%	128 85.9%	255 86.4%
RWANDA	19 13%	21 14.1%	40 13.6%

Outcome Measures

1. Primary Outcome

Title	Cure Rate for Ascaris Lumbricoides at the End of Double-blind Treatment Period
Description	Cure is defined as a post-treatment egg count of zero in participants who had a positive egg count at baseline.
Time Frame	At Visit 3 (Day 19) of Double-blind treatment period

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized participants with a pretreatment stool sample positive for 1 or more worms of interest. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Double-blind Placebo	Double-blind Mebendazole 500 mg
Arm/Group Description	Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).
Measure Participants	81	86
Number (95% Confidence Interval) [percentage of participants]	11.1 7.6%	83.7 56.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind Placebo, Double-blind Mebendazole 500 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Primary Outcome

Title	Cure Rate for Trichuris Trichiura at the End of Double-blind Treatment Period
Description	Cure is defined as a post-treatment egg count of zero in participants who had a positive egg count at baseline.
Time Frame	At Visit 3 (Day 19) of Double-blind treatment period

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants with a pretreatment stool sample positive for 1 or more worms of interest. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Double-blind Placebo	Double-blind Mebendazole 500 mg
Arm/Group Description	Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).
Measure Participants	119	124
Number (95% Confidence Interval) [percentage of participants]	7.6 5.2%	33.9 22.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind Placebo, Double-blind Mebendazole 500 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Primary Outcome

Title	Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Double-Blind Treatment Period
Description	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.
Time Frame	Up to Visit 3 (Day 19 +/-2)

Outcome Measure Data

Analysis Population Description

The safety analysis set consisted of all randomized participants who received 1 dose of study agent (mebendazole or placebo) at baseline. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Double-blind Placebo	Double-blind Mebendazole 500 mg
Arm/Group Description	Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).
Measure Participants	140	144
Number [participants]	8 5.5%	9 6%

4. Secondary Outcome

Title	Egg Count Reduction Rate (Percent) for Ascaris Lumbricoides Infestation at the End of Double-blind Treatment Period
Description	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.
Time Frame	Baseline and Day 19 (Visit 3) at the End of Double-blind Treatment Period

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants with a pretreatment stool sample positive for 1 or more worms of interest. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Double-blind Placebo	Double-blind Mebendazole 500 mg
Arm/Group Description	Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).
Measure Participants	81	86
Number [percent change in egg count]	-19.2 (20684.03)	-97.9 (23476.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind Placebo, Double-blind Mebendazole 500 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Egg Count Reduction Rate (Percent) for Trichuris Trichiura Infestation at the End of Double-blind Treatment Period
Description	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.
Time Frame	Baseline and Day 19 (Visit 3) at the End of Double-blind Treatment Period

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants with a pretreatment stool sample positive for 1 or more worms of interest. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Double-blind Placebo	Double-blind Mebendazole 500 mg
Arm/Group Description	Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).
Measure Participants	119	124
Number [percent change in egg count]	-10.5 (930.05)	-59.7 (1256.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind Placebo, Double-blind Mebendazole 500 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of Mebendazole
Description	The Cmax is the maximum plasma concentration.
Time Frame	Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included all randomized participants who received at least 1 dose of the study drug and had valid pharmacokinetic profile. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Mebendazole: Group 1 (1 to <3 Years)	Mebendazole: Group 2 (3 to 6 Years)	Mebendazole: Group 3 (7 to 16 Years)
Arm/Group Description	Group 1 represents pharmacokinetic analysis set which included participants with age group 1 to less than (<) 3 years and received Mebendazole 500 milligram (mg).	Group 2 represents pharmacokinetic analysis set which included participants with age group 3 to 6 years and received Mebendazole 500 mg.	Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Measure Participants	22	12	10
Mean (Standard Deviation) [nanogram per Milliliters (ng/mL)]	210.0 (212.0)	49.9 (26.8)	34.2 (13.8)

7. Primary Outcome

Title	Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Open-Label Treatment Period
Description	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.
Time Frame	At Visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3)

Outcome Measure Data

Analysis Population Description

The open-label follow-up safety analysis set consisted of all randomized participants who received a 500-mg chewable tablet of mebendazole at Visit 3. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Open-label Mebendazole 500 mg
Arm/Group Description	Mebendazole 500-mg chewable tablet was administered in an open label manner at visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3).
Measure Participants	278
Number [participants]	7 4.8%

8. Secondary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax) of Mebendazole
Description	The Time to Reach Maximum Plasma Concentration (Tmax) is time to reach the maximum plasma concentration.
Time Frame	Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

Outcome Measure Data

Analysis Population Description

PK population included all randomized participants who received at least 1 dose of the study drug and had valid pharmacokinetic profile. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Mebendazole: Group 1 (1 to <3 Years)	Mebendazole: Group 2 (3 to 6 Years)	Mebendazole: Group 3 (7 to 16 Years)
Arm/Group Description	Group 1 represents pharmacokinetic analysis set which included participants with age group 1 to less than (<) 3 years and received Mebendazole 500 milligram (mg).	Group 2 represents pharmacokinetic analysis set which included participants with age group 3 to 6 years and received Mebendazole 500 mg.	Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Measure Participants	22	12	10
Mean (Full Range) [hours]	2.5	2	3

9. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours (AUC8h) of Mebendazole
Description	The (AUC8h) is the area under the plasma concentration-time curve from time 0 to 8 hours Post-dose.
Time Frame	Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

Outcome Measure Data

Analysis Population Description

PK population included all randomized participants who received at least 1 dose of the study drug and had valid pharmacokinetic profile. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Mebendazole: Group 1 (1 to <3 Years)	Mebendazole: Group 2 (3 to 6 Years)	Mebendazole: Group 3 (7 to 16 Years)
Arm/Group Description	Group 1 represents pharmacokinetic analysis set which included participants with age group 1 to less than (<) 3 years and received Mebendazole 500 milligram (mg).	Group 2 represents pharmacokinetic analysis set which included participants with age group 3 to 6 years and received Mebendazole 500 mg.	Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Measure Participants	21	9	10
Mean (Standard Deviation) [nanogram hour per Milliliters(ng*h/mL)]	697 (367)	242 (139)	182 (66.3)

10. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) of Mebendazole
Description	The (AUC [0-last]) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.
Time Frame	Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

Outcome Measure Data

Analysis Population Description

PK population included all randomized participants who received at least 1 dose of the study drug and had valid pharmacokinetic profile. Here 'N' signifies number of participants analysed for this outcome measure.

Arm/Group Title	Mebendazole: Group 1 (1 to <3 Years)	Mebendazole: Group 2 (3 to 6 Years)	Mebendazole: Group 3 (7 to 16 Years)
Arm/Group Description	Group 1 represents pharmacokinetic analysis set which included participants with age group 1 to less than (<) 3 years and received Mebendazole 500 milligram (mg).	Group 2 represents pharmacokinetic analysis set which included participants with age group 3 to 6 years and received Mebendazole 500 mg.	Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Measure Participants	22	12	10
Mean (Standard Deviation) [ng*h/mL]	1320 (844)	416 (215)	387 (190)

Adverse Events

Time Frame	Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Arm/Group Title	Double-blind Placebo		Double-blind Mebendazole 500 mg		OL Mebendazole 500 mg
Arm/Group Description	Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).		Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).		Mebendazole 500-mg chewable tablet was administered in an open label manner at visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3).
All Cause Mortality
	Double-blind Placebo		Double-blind Mebendazole 500 mg		OL Mebendazole 500 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Double-blind Placebo		Double-blind Mebendazole 500 mg		OL Mebendazole 500 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/140 (0%)		0/144 (0%)		0/278 (0%)
Other (Not Including Serious) Adverse Events
	Double-blind Placebo		Double-blind Mebendazole 500 mg		OL Mebendazole 500 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/140 (5.7%)		9/144 (6.3%)		7/278 (2.5%)
Eye disorders
Night Blindness	1/140 (0.7%)		0/144 (0%)		0/278 (0%)
Gastrointestinal disorders
Abdominal Distension	1/140 (0.7%)		2/144 (1.4%)		0/278 (0%)
Abdominal Pain	1/140 (0.7%)		1/144 (0.7%)		1/278 (0.4%)
Diarrhoea	0/140 (0%)		0/144 (0%)		2/278 (0.7%)
Vomiting	0/140 (0%)		0/144 (0%)		1/278 (0.4%)
Infections and infestations
Conjunctivitis	1/140 (0.7%)		0/144 (0%)		0/278 (0%)
Conjunctivitis Bacterial	1/140 (0.7%)		0/144 (0%)		0/278 (0%)
Gastroenteritis	0/140 (0%)		1/144 (0.7%)		0/278 (0%)
Malaria	0/140 (0%)		0/144 (0%)		1/278 (0.4%)
Nasopharyngitis	2/140 (1.4%)		1/144 (0.7%)		0/278 (0%)
Pneumonia	0/140 (0%)		0/144 (0%)		1/278 (0.4%)
Tinea Infection	0/140 (0%)		1/144 (0.7%)		0/278 (0%)
Tonsillitis	1/140 (0.7%)		0/144 (0%)		0/278 (0%)
Injury, poisoning and procedural complications
Soft Tissue Injury	0/140 (0%)		0/144 (0%)		1/278 (0.4%)
Metabolism and nutrition disorders
Vitamin A Deficiency	0/140 (0%)		1/144 (0.7%)		0/278 (0%)
Nervous system disorders
Headache	0/140 (0%)		0/144 (0%)		1/278 (0.4%)
Respiratory, thoracic and mediastinal disorders
Cough	2/140 (1.4%)		1/144 (0.7%)		0/278 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/140 (0%)		0/144 (0%)		1/278 (0.4%)
Rash Pruritic	0/140 (0%)		1/144 (0.7%)		0/278 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.