Comparative Efficacy of Different Mebendazole Polymorphs in the Treatment of Soil-transmitted Helminth Infections

Study Overview
=================
Brief Summary
-----------------
Mebendazole tablets which are produced by most pharmaceutical manufacturers, including the State Pharmaceutical Manufacturing Corporation (SPMC) of Sri Lanka, contain a mixture of polymorphs A and C. However, there is some evidence to show that mebendazole polymorph C is the only form effective against the soil-transmitted helminths. This protocol describes a stratified, randomized, placebo-controlled trial that examined the efficacy of different mebendazole polymorphs produced by the SPMC in the treatment of hookworm infections.

Detailed Description
-----------------
Mebendazole has three polymorphic forms, identified as A, B and C. All of them are in accord with the US Pharmacopeia specifications (USP XXI) but they have distinct physiochemical characteristics (Himmelreich et al, 1977) and different therapeutic activities in experimentally infected mice with Trichinella spiralis infections (Rodriguez-Caabeiro et al, 1987). The original mebendazole tablets which were used to treat human infections had more than 90% of polymorph C (Van den Bossche et al, 1982), but most pharmacopeias currently do not specify the proportion of polymorph C that a tablet of mebendazole should contain, and the assay specified for measurement of the active ingredient measures all polymorphs together. There is some evidence to show that unlike polymorph C, polymorph A is ineffective in the treatment of hookworm and whipworm infections (Charoenlarp et al, 1993). The State Pharmaceutical Manufacturing Corporation of Sri Lanka produces both 500 mg and 100 mg tablets of mebendazole according to specifications laid down in the US Pharmacopeia. These tablets contain a mixture of polymorphs A and C. It is possible that increasing the content of mebendazole polymorph C in single dose tablets may improve cure rates and egg reduction rates, especially against hookworm and whipworm infections, where much variation in efficacy has been observed.

Official Title
-----------------
Comparative Efficacy of Different Mebendazole Polymorphs in the Treatment of Soil-transmitted Helminth Infections

Conditions
-----------------
Necator Americanus Infection

Intervention / Treatment
-----------------
* Drug: Mebendazole polymorph A and C 500 mg
* Drug: Mebendazole polymorph C
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Necator americanus infection, as determined by examination of a single faecal smear, alone or with Ascaris lumbricoides or Trichuris trichiura Exclusion Criteria: Children below the age of 2 years Pregnant women Individuals with diarrhea on day of treatment

Ages Eligible for Study
-----------------
Minimum Age: 3 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka | Drug: Placebo<br>* Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka<br>|
| Active Comparator: Mebendazole polymorph A and C 500 mg<br>Mebendazole tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg of mebendazole as a 50:50 mixture of Polymorphs A and C | Drug: Mebendazole polymorph A and C 500 mg<br>* Mebendazole tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg of mebendazole as a 50:50 mixture of Polymorphs A and C<br>* Other names: Lot FG10M01;|
| Experimental: Mebendazole polymorph C 500 mg<br>Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone | Drug: Mebendazole polymorph C<br>* Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone<br>* Other names: Lot FG10H01;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure Rate | Cure rate={(Number positive pretreatment - Number positive posttreatment)÷(Number positive pretreatment)}×100 | Two weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Faecal Egg Count Reduction 1 (FECR1) | FECR1= {[(Arithmetic mean of pretreatment egg counts)-(arithmetic mean of posttreatment egg counts)]÷(arithmetic mean of pretreatment egg counts)}×100 | Two weeks | 
| Faecal Egg Count Reduction 2 (FECR2) | FECR2=〈Arithmetic mean {[(pretreatment egg count)-(posttreatment egg count)]÷(pretreatment egg count)}〉×100 | Two weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hookworm, Necator americanus, Mebendazole