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
  Purpose

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 Intervention Phase
Healthy Subjects
Drug: AD 452 (+) mefloquine
Drug: Racemic Mefloquine
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I Randomised, Double-Blind Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine

Resource links provided by NLM:


Further study details as provided by Treague Ltd:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • The comparative pharmacokinetics of AD 452 [(+)mefloquine] and racemic mefloquine [ Time Frame: Single dose ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: June 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Drug: Placebo
Over-encapsulated placebo to maintain blinding

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00931697

Locations
United Kingdom
LCG Bioscience
Cambridge, Cambridgeshire, United Kingdom, CB23 2TN
Sponsors and Collaborators
Treague Ltd
Medicines for Malaria Venture
Investigators
Study Director: Robert Tansley, MBBS Treague Ltd
  More Information

Additional Information:
No publications provided

Responsible Party: Dr Robert Tansley, Treague Ltd
ClinicalTrials.gov Identifier: NCT00931697     History of Changes
Other Study ID Numbers: P-AD452-023
Study First Received: June 29, 2009
Last Updated: July 30, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Treague Ltd:
Mefloquine
Malaria
(+) Mefloquine
Pharmacokinetics

Additional relevant MeSH terms:
Mefloquine
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014