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

Phase 3

Completed

Interventions: Drug: Mebendazole polymorph A and C 500 mg
Drug: Placebo
Drug: Mebendazole polymorph C

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.

Recruitment & Eligibility

Inclusion Criteria

Necator americanus infection, as determined by examination of a single faecal smear, alone or with Ascaris lumbricoides or Trichuris trichiura

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Mebendazole polymorph A and C 500 mg	Mebendazole polymorph A and C 500 mg	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
Placebo	Placebo	Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka
Mebendazole polymorph C 500 mg	Mebendazole polymorph C	Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone

Primary Outcome Measures

Name	Time	Method
Cure Rate	Two weeks	Cure rate={(Number positive pretreatment - Number positive posttreatment)÷(Number positive pretreatment)}×100

Secondary Outcome Measures

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

Locations (2): Agalawatta Plantations PLC
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Nivitigala, Sabragamuwa, Sri Lanka
Lellopitiya Estate, Hapugastenne Plantations PLC
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Ratnapura, Sabragamuwa, Sri Lanka