A Phase I Randomised, Double-Blind Study to Investigate the Safety, Tolerability and Pharmacokinetics of AD 452 [(+)-Mefloquine] Compared With Racemic Mefloquine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Treague Ltd
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
AD 452 (+) mefloquine
干预措施: AD 452 (+) mefloquine (Drug)
Racemic mefloquine
干预措施: Racemic Mefloquine (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
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.
时间窗: Following single dose
次要结局
- The comparative pharmacokinetics of AD 452 [(+)mefloquine] and racemic mefloquine(Single dose)