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

Healthy Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00931697
• Other study ID #: P-AD452-023
• Status: Completed
• Phase: Phase 1
• First received: June 29, 2009
• Last updated: July 30, 2010
• Start date: June 2009
• Est. completion date: November 2009

Study information

• Verified date: July 2010
• Source: Treague Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• AD 452 (+) mefloquine
Single dose delivered as over-encapsulated tablet at ascending doses
• Racemic Mefloquine
Single dose delivered as over-encapsulated tablet at ascending dose
• Placebo
Over-encapsulated placebo to maintain blinding

Locations

Country	Name	City	State
United Kingdom	LCG Bioscience	Cambridge	Cambridgeshire

Sponsors (2)

Lead Sponsor	Collaborator
Treague Ltd	Medicines for Malaria Venture

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Following single dose	Yes
Secondary	The comparative pharmacokinetics of AD 452 [(+)mefloquine] and racemic mefloquine		Single dose	No

External Links

•   Medicines for Malaria Venture website