Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine
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|ClinicalTrials.gov Identifier: NCT00931697|
Recruitment Status : Completed
First Posted : July 2, 2009
Last Update Posted : August 3, 2010
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.
|Condition or disease||Intervention/treatment||Phase|
|Healthy Subjects||Drug: AD 452 (+) mefloquine Drug: Racemic Mefloquine Drug: Placebo||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||46 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||A Phase I Randomised, Double-Blind Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine|
|Study Start Date :||June 2009|
|Actual Primary Completion Date :||November 2009|
|Actual Study Completion Date :||November 2009|
|Experimental: AD 452 (+) mefloquine||
Drug: AD 452 (+) mefloquine
Single dose delivered as over-encapsulated tablet at ascending doses
|Active Comparator: Racemic mefloquine||
Drug: Racemic Mefloquine
Single dose delivered as over-encapsulated tablet at ascending dose
|Placebo Comparator: Placebo||
Over-encapsulated placebo to maintain blinding
- 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 ]
- The comparative pharmacokinetics of AD 452 [(+)mefloquine] and racemic mefloquine [ Time Frame: Single dose ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00931697
|Cambridge, Cambridgeshire, United Kingdom, CB23 2TN|
|Study Director:||Robert Tansley, MBBS||Treague Ltd|