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

Necator Americanus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01350271
• Other study ID #: P39/04/2010
• Secondary ID: Ragama ERC
• Status: Completed
• Phase: Phase 3
• First received: May 6, 2011
• Last updated: April 18, 2013
• Start date: May 2011
• Est. completion date: June 2011

Study information

• Verified date: April 2013
• Source: University of Kelaniya
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sri Lanka: Ministry of Healthcare & Nutrition
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years and older

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:

• Children below the age of 2 years

• Pregnant women

• Individuals with diarrhea on day of treatment

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Helminthiasis
• Infection
• Necator Americanus Infection

Intervention

Drug:
• 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
• Mebendazole polymorph C
Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone
• Placebo
Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka

Locations

Country	Name	City	State
Sri Lanka	Agalawatta Plantations PLC	Nivitigala	Sabragamuwa
Sri Lanka	Lellopitiya Estate, Hapugastenne Plantations PLC	Ratnapura	Sabragamuwa

Sponsors (1)

Lead Sponsor	Collaborator
University of Kelaniya

Country where clinical trial is conducted

Sri Lanka, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cure Rate	Cure rate={(Number positive pretreatment - Number positive posttreatment)÷(Number positive pretreatment)}×100	Two weeks	No
Secondary	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	No
Secondary	Faecal Egg Count Reduction 2 (FECR2)	FECR2=	Two weeks	No