A Single-Blind, Placebo-Controlled, Randomized First Time in Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Dose Escalation of GSK932121 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Evidence of safety as determined by assessing adverse events, vital signs, spirometry, ECGs, telemetry, renal biomarkers, safety labs, and physical examination
研究概览
简要总结
The purpose of this study is to determine if the study drug (antimalarial medication) is safe when given to healthy subjects as a single dose or as repeated doses, to understand the effect of food on single doses of study drug and to determine if the study drug has an effect on other approved medications such as rosiglitazone and rosuvastatin.
详细描述
Malaria is a type of parasitic infection, common in tropical and subtropical regions of the world, including parts of the Americas, Asia, and Africa. In recent years there has been a rapid spread of drug resistant malaria which makes it necessary to develop new antimalarial treatments. In animal studies, GSK932121 is shown to be able to kill the malaria parasite and is fully active against drug resistant malaria parasites. It is hoped that information collected on this study will lead to an improved treatment for malaria.
This is a first time in human fusion study which has 3 parts:
Part A - single dose escalation/ food effect: a study where the study drug is given once only- first at the lowest dose of in a group of participants and the dose increased only if the previous dose is found to be safe. It also looks at the effect of food on the study drug in the body Part B - repeat dose escalation: a study where the study drug will be given daily for up to 7 days - first at a lower dose in a group of participants and the dose increased for the next group only if the previous dose is found to be safe and Part B - drug-drug interaction: a study where the study drug will be given daily for up to 7 days at a dose determined to be safe in previous groups of participants and looking at the effect of the study drug on other specific approved medications (such as rosiglitazone--a diabetic medication and rosuvastatin--a cholesterol lowering medication) in the body.
Safety will be assessed by measurement of vital signs, cardiac monitoring, spirometry, collection of adverse event assessments, renal biomarkers and laboratory safety tests.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
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
- •Male or female between 18 and 50 years of age, inclusive
- •Females of non-childbearing potential (as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea
- •Body weight > 50 kg and BMI within the range 19 - 31 kg/m2 (inclusive)
- •QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block
排除标准
- •Positive pre-study drug/alcohol screen
- •Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- •A positive test for HIV antibody
- •History of regular alcohol consumption within 6 months of the study
- •Participation in a clinical trial with an investigational product within 30 days or 5 half-lives of the investigational product (whichever is longer) prior to start of the new study
- •Exposure to more than four new drugs or within 12 months prior to the first dosing day
- •Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication
- •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that would be contraindicated
- •Donation of blood or blood products in excess of 500 mL within a 56 day period.
- •Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
- •Lactating females.
- •Unwillingness or inability to follow the procedures outlined in the protocol.
- •History of sensitivity to heparin or history of heparin-induced thrombocytopenia if heparin is used to maintain the patency of an intravenous cannula.
- •Asthma or a history of asthma
- •Smoking or history or regular use of tobacco- or nicotine-containing products within 2 months prior to screening
- •Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
研究组 & 干预措施
Single Dose, Repeat Dose, Drug-Drug Interaction
GSK932121 or placebo will be administered as a single dose with or without food in a dose escalation manner. Once the results from the single dose is obtained and reviewed, GSK932121 or placebo will be administered as a repeat dose. The results from each repeat dose level will be reviewed prior to determining the next repeat dose level.
To better understand the effect of GSK932121 on rosiglitazone and rosuvastatin, a drug-drug interaction arm will also be investigated in this study. Rosiglitazone and rosuvastatin will be administered alone, then GSK932121 will be given as a repeat dose. Rosiglitazone and rosuvastatin will then be administered in combination with GSK932121.
干预措施: GSK932121; Rosiglitazone; Rosuvastatin (Drug)
结局指标
主要结局
Evidence of safety as determined by assessing adverse events, vital signs, spirometry, ECGs, telemetry, renal biomarkers, safety labs, and physical examination
时间窗: Part A: 3-4 months; Part B: ~1 month
次要结局
- Plasma or blood concentrations of study drug(Part A: 3-4 months; Part B: ~1 month)