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

University of Kelaniya

Status and phase: Completed; Phase 3

Conditions: Necator Americanus Infection

Treatments: Drug: Mebendazole polymorph A and C 500 mg; Drug: Placebo; Drug: Mebendazole polymorph C

Study type: Interventional

Funder types: Other

Identifiers

NCT01350271

Ragama ERC (Registry Identifier)

P39/04/2010

Details and patient eligibility

About

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.

Full 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.

Enrollment: 214 patients

Sex: All

Ages: 3+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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214 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka

Treatment:

Drug: Placebo

Mebendazole polymorph A and C 500 mg

Active Comparator group

Description:

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

Treatment:

Drug: Mebendazole polymorph A and C 500 mg

Mebendazole polymorph C 500 mg

Experimental group

Description:

Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone

Treatment:

Drug: Mebendazole polymorph C