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

This study has been completed.
Sponsor:
Collaborator:
Medicines for Malaria Venture
Information provided by:
Treague Ltd
ClinicalTrials.gov Identifier:
NCT00931697
First received: June 29, 2009
Last updated: July 30, 2010
Last verified: July 2010

June 29, 2009
July 30, 2010
June 2009
November 2009   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00931697 on ClinicalTrials.gov Archive Site
The comparative pharmacokinetics of AD 452 [(+)mefloquine] and racemic mefloquine [ Time Frame: Single dose ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine
A Phase I Randomised, Double-Blind 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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Healthy Subjects
  • 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
  • Experimental: AD 452 (+) mefloquine
    Intervention: Drug: AD 452 (+) mefloquine
  • Active Comparator: Racemic mefloquine
    Intervention: Drug: Racemic Mefloquine
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
November 2009
November 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT00931697
P-AD452-023
Yes
Dr Robert Tansley, Treague Ltd
Treague Ltd
Medicines for Malaria Venture
Study Director: Robert Tansley, MBBS Treague Ltd
Treague Ltd
July 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP