Pharmacokinetics of Plasma Lopinavir/Ritonavir Over a 12 Hour Dosing Interval Following Administration of 400/100, 200/150, and 200/50 mg Twice Daily to HIV-negative Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).
研究概览
简要总结
The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval, following administration to male and female HIV-negative healthy volunteers of:
- Lopinavir/ritonavir 400/100 mg twice daily
- Lopinavir/ritonavir 200/150 mg twice daily
- Lopinavir/ritonavir 200/50 mg twice daily
详细描述
Data during the development of lopinavir/ritonavir showed that lower drug doses had similar efficacy to the standard dose of 400/100mg twice daily. Lower drug doses are also associated with limited toxicity and cost.
The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir following administration to male and female HIV-negative volunteers of 400/100mg, 200/150mg and 200/50mg lopinavir/ritonavir twice daily. Each dosing phase will last for 7 days and each phase will be separated by a 7-day wash-out period. Pharmacokinetic evaluations will be made over a 12-hour interval at the end of each dosing phase.
Healthy subjects as determined by their medical history and physical examinations will be eligible to participate in the study. HIV-positive subjects will not be recruited as there is a risk that HIV-resistant mutations will be selected by an experimentally reduced dose of lopinavir/ritonavir. There is no reason to presume that there is any meaningful difference in the metabolic processing of lopinavir/ritonavir between HIV-infected and HIV-uninfected people.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects must meet all of the following inclusion criteria within 28 days prior to the baseline visit:
- •The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
- •Male or non-pregnant, non-lactating females
- •Between 18 to 65 years, inclusive
- •Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
- •Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month after the study
排除标准
- •Any significant acute or chronic medical illness
- •Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- •Positive blood screen for hepatitis B core and/or C antibodies and/or hepatitis B surface antigen
- •Positive blood screen for HIV-1 and/or 2 antibodies
- •Current or recent (within 3 months) gastrointestinal disease
- •Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
- •Exposure to any investigational drug or placebo within 3 months of first dose of study drug
- •Consumption of grapefruit, or Seville oranges or any grapefruit or Seville orange containing product within one week of first dose of study drug and for the duration of the study
- •Use of any other drugs, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
- •Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 30 days after the end of the treatment period
- •Previous allergy to any of the constituents of the pharmaceuticals administered in this trial
研究组 & 干预措施
LPV/r 400/100 mg
Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))
干预措施: lopinavir/ritonavir (Drug)
LPV/r 200/150 mg
Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID)
干预措施: lopinavir/ritonavir (Drug)
LPV/r 200/50 mg
Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)
干预措施: lopinavir/ritonavir (Drug)
结局指标
主要结局
Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).
时间窗: at the end of each 7-day dosing phase
Pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval following administration of lopinavir/ritonavir 400/100mg, 200/150mg and 200/50mg twice daily.
次要结局
- Adverse Events(Up to 11 weeks from screening to final study visit)