Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine
Information source: Treague Ltd
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy Subjects
Intervention: AD 452 (+) mefloquine (Drug); Racemic Mefloquine (Drug); Placebo (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Treague Ltd Official(s) and/or principal investigator(s): Robert Tansley, MBBS, Study Director, Affiliation: Treague Ltd
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: 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.
Secondary outcome: The comparative pharmacokinetics of AD 452 [(+)mefloquine] and racemic mefloquine
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
LCG Bioscience, Cambridge, Cambridgeshire CB23 2TN, United Kingdom
Additional Information
Medicines for Malaria Venture website
Starting date: June 2009
Last updated: July 30, 2010
|