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Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine

NCT00931697 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 46

Last updated 2010-08-03

No results posted yet for this study

Summary

Mefloquine is a quinolinemethanol antimalarial that is effective as therapy and prophylaxis for all species of malaria infecting humans, including multi-drug resistant Plasmodium falciparum. The marketed anti-malaria drug consists of two enantiomers of mefloquine.

Mefloquine's clinical utility has been impaired by its association with neuropsychiatric side effects. The pharmacological basis of mefloquine's side effects is not known but two of the most reported hypotheses relate to its action on (i) the adenosine receptor and (ii) its effect on the cholinesterase enzyme. For both of these mechanisms, there is a significant stereoselective activity of the two enantiomers. In vitro studies show that the (-) isomer is 50-100 fold more potent towards adenosine receptors compared with the (+) isomer. In addition, (-)-mefloquine has considerably more anti-cholinesterase activity. It has therefore been hypothesised that (+)-mefloquine may have a better central nervous system (CNS) safety profile compared with either the racemate or (-)-mefloquine.

This study is a randomized, ascending dose, double-blind, active and placebo-controlled, parallel group study in healthy male and female volunteers designed to investigate this hypothesis and to describe the comparative pharmacokinetics of the racemate and the single enantiomer.

Conditions

  • Healthy Subjects

Interventions

DRUG

AD 452 (+) mefloquine

Single dose delivered as over-encapsulated tablet at ascending doses

DRUG

Racemic Mefloquine

Single dose delivered as over-encapsulated tablet at ascending dose

DRUG

Placebo

Over-encapsulated placebo to maintain blinding

Sponsors & Collaborators

  • Medicines for Malaria Venture

    collaborator OTHER

  • Treague Ltd

    lead INDUSTRY

Principal Investigators

  • Robert Tansley, MBBS · Treague Ltd

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
50 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2009-06-30
Primary Completion
2009-11-30
Completion
2009-11-30

Countries

  • United Kingdom

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00931697 on ClinicalTrials.gov