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NCT Number: NCT00931697

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

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.

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Key information

Conditions

Healthy Subjects Infections Malaria Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

LCG Bioscience

Cambridge, Cambridgeshire, CB23 2TN, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • A BMI of between 19 and 28
  • Negative urine drugs of abuse and breath alcohol test
  • Willing to use double barrier contraception for 13 weeks after administration of study drug

Exclusion criteria

  • Pregnant or lactating females
  • Existence of any surgical or medical condition which, in the judgement of the Principal Investigator, might interfere with the absorption and disposition of the drug or with the aim of the study including clinically significant lactose intolerance
  • Receipt of prescription medication within 21 days of the first study day or over the counter medication (with the exception of multi-vitamins or paracetamol) within 1 week before the planned dosing date without prior approval
  • Definite or suspected personal or family history of adverse drug reaction or hypersensitivity to drugs with a chemical structure similar to AD 452
  • Participation in a clinical study within the previous 12 weeks
  • A history of sensitivity to antimalarial or related compounds
  • Definite or suspected personal or family history of adverse drug reaction or hypersensitivity to drugs with a chemical structure similar to AD 452
  • Active depression or a recent history of depression or generalised anxiety disorder
  • Any personal history of psychosis or schizophrenia or other major psychiatric disorders or convulsions
  • Previous exposure to racemic mefloquine

Treatment and study plan

AD 452 (+) mefloquine

Drug

Single dose delivered as over-encapsulated tablet at ascending doses

Racemic Mefloquine

Drug

Single dose delivered as over-encapsulated tablet at ascending dose

Placebo

Drug

Over-encapsulated placebo to maintain blinding

Primary outcomes

  1. The dose-concentration-effect relationship of AD 452 [(+)-mefloquine] for safety and toleration in comparison with that of racemic mefloquine across a range of potentially therapeutic doses and concentrations.

    Time frame: Following single dose

Secondary outcomes

  1. The comparative pharmacokinetics of AD 452 [(+)mefloquine] and racemic mefloquine

    Time frame: Single dose

Sponsors and collaborators

Lead sponsor

Treague Ltd

Industry

Collaborators

  • Medicines for Malaria Venture

Registry information

Official study title

A Phase I Randomised, Double-Blind Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine

Important dates

Study start
2009
Primary completion
2009
Study completion
2009
First posted
Jul 2, 2009
Registry last updated
Aug 3, 2010

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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