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

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.

Study Overview

• Status: Completed
• Conditions: Necator Americanus Infection
• Intervention / Treatment: Drug: Placebo; Drug: Mebendazole polymorph A and C 500 mg; Drug: Mebendazole polymorph C

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.

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 3

Contacts and Locations

Study Locations

• Sri Lanka
  • Sabragamuwa
    • Nivitigala, Sabragamuwa, Sri Lanka
      • Agalawatta Plantations PLC
    • Ratnapura, Sabragamuwa, Sri Lanka
      • Lellopitiya Estate, Hapugastenne Plantations PLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka	Drug: Placebo; Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka
Active Comparator: 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	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; Other Names: Lot FG10M01
Experimental: Mebendazole polymorph C 500 mg; 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; Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone; 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

Collaborators and Investigators

• Sponsor: University of Kelaniya
• Investigators: Principal Investigator: Nilanthi R de Silva, MD, Faculty of Medicine, University of Kelaniya, Sri Lanka

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: May 6, 2011
• First Submitted That Met QC Criteria: May 6, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Estimate): April 22, 2013
• Last Update Submitted That Met QC Criteria: April 18, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Hookworm; Necator americanus; Mebendazole
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Parasitic Diseases; Infections; Communicable Diseases; Helminthiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Mebendazole; Piperazine; Piperazine citrate; DMP 777
• Other Study ID Numbers: P39/04/2010; Ragama ERC (Registry Identifier: www.clinicaltrials.org)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No