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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
N R de Silva, University of Kelaniya
ClinicalTrials.gov Identifier:
NCT01350271
First received: May 6, 2011
Last updated: April 18, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Necator Americanus Infection
Drug: Mebendazole polymorph A and C 500 mg
Drug: Mebendazole polymorph C
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparative Efficacy of Different Mebendazole Polymorphs in the Treatment of Soil-transmitted Helminth Infections

Resource links provided by NLM:


Further study details as provided by University of Kelaniya:

Primary Outcome Measures:
  • Cure Rate [ Time Frame: Two weeks ] [ Designated as safety issue: No ]
    Cure rate={(Number positive pretreatment - Number positive posttreatment)÷(Number positive pretreatment)}×100


Secondary Outcome Measures:
  • Faecal Egg Count Reduction 1 (FECR1) [ Time Frame: Two weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: Two weeks ] [ Designated as safety issue: No ]
    FECR2=〈Arithmetic mean {[(pretreatment egg count)-(posttreatment egg count)]÷(pretreatment egg count)}〉×100


Enrollment: 214
Study Start Date: May 2011
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Lot FG10H01

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.

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01350271

Locations
Sri Lanka
Agalawatta Plantations PLC
Nivitigala, Sabragamuwa, Sri Lanka
Lellopitiya Estate, Hapugastenne Plantations PLC
Ratnapura, Sabragamuwa, Sri Lanka
Sponsors and Collaborators
University of Kelaniya
Investigators
Principal Investigator: Nilanthi R de Silva, MD Faculty of Medicine, University of Kelaniya, Sri Lanka
  More Information

No publications provided

Responsible Party: N R de Silva, Professor of Parasitology, University of Kelaniya
ClinicalTrials.gov Identifier: NCT01350271     History of Changes
Other Study ID Numbers: P39/04/2010, Ragama ERC
Study First Received: May 6, 2011
Results First Received: August 23, 2011
Last Updated: April 18, 2013
Health Authority: Sri Lanka: Ministry of Healthcare & Nutrition

Keywords provided by University of Kelaniya:
Hookworm
Necator americanus
Mebendazole

Additional relevant MeSH terms:
Communicable Diseases
Helminthiasis
Infection
Parasitic Diseases
Mebendazole
Piperazine
Piperazine citrate
Anthelmintics
Anti-Infective Agents
Antimitotic Agents
Antinematodal Agents
Antineoplastic Agents
Antiparasitic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014