A Study to Assess Relative Bioavailability and Food Effect of New Formulations of GSK2248761
2020年3月25日 更新者:ViiV Healthcare
A Single-center, Randomized, Two Part, Open-label, Crossover Study to Assess the Relative Bioavailability and Food Effect of New Formulations of GSK2248761 in Healthy Adult Subjects
This is a single-center, randomized, two part, open-label, crossover study in healthy adult subjects to assess the effect of up to three formulations on the relative bioavailability of GSK2248761 100mg administered with and without food.
Part A will evaluate two new formulations compared to the current formulation.
Part B will evaluate one additional formulation if the bioavailability of the two formulations in Part A do not meet pre-specified criteria.
Safety evaluations and serial PK samples will be collected during each treatment period.
A follow-up visit will occur 7-10 days after the last dose of study drug.
研究概览
地位
完全的
研究类型
介入性
注册 (实际的)
24
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
-
New York
-
Buffalo、New York、美国、14202
- GSK Investigational Site
-
-
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 50年 (成人)
接受健康志愿者
是的
有资格学习的性别
全部
描述
Inclusion Criteria:
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECGs.
- Male or female between 18 and 50 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:
- Is pre-menopausal with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy, or is post-menopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating hormone (FSH) level will be performed to confirm a post-menopausal status. For this study, FSH levels > 40 MlU/ml is confirmatory.
- Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
- Body weight greater than or equal to 50 kg for men and greater than or equal to 45 kg for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Exclusion Criteria:
- As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit for the study.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
- History of regular alcohol consumption within 6 months of the study.
- Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final pharmacokinetic sample during each treatment period.
- History or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
- History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or any clinically significant cardiac disease.
- History/evidence of clinically significant pulmonary disease.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy should be excluded.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- The subject has received GSK2248761 in a previous clinical trial.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. Note: this does not include plasma donation.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
- AST, ALT, alkaline phosphatase and bilirubin greater than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
- Lactating females.
- The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects at Screening and predose Day 1.
- Cardiac conduction abnormalities on a single 12-lead ECG at screening or predose Day 1.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:交叉作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:Part A
Subjects will be randomized in a three way crossover design to either a single dose of GSK2248761 100mg Gelucire capsule administered with food and a single dose of 100mg of formulation 1 or a single dose of 100mg of formulation 3 administered in the fed and fasted state
|
100mg GSK2248761 formulation 1- fasted 100mg GSK2248761 formulation 1 - with food (moderate fat meal)
GSK2248761 100mg Gelucire reference capsule with food
100mg GSK2248761 formulation 3 fasted 100mg GSK2248761 formulation 3 with food (moderate fat meal)
|
|
实验性的:Part B
A total of twelve subjects who complete Part A will participate in Part B. Subjects from Part A will be asked to participate on a first come first serve basis until there are 12 subjects, at which time enrolment to Part B will be closed.
Part B will be a 2 way cross over study design.
Subjects will be randomized to one of a single dose of GSK2248761 100mg Formulation 2 or 4 (based on the evaluation of Part A data) administered with food or in the fasted state.
Subjects in Part B will not receive the reference formulation since they previously received this in Part A
|
100mg GSK2248761 formulation 2 or 4 - fasted 100mg GSK2248761 formulation 2 or 4 - with food (moderate fat meal)
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Area under the concentration-time curve zero to infinity of plasma GSK2248761
大体时间:Up to 5 weeks
|
Plasma samples will be collected for the analysis of AUC (0-inf) of GSK2248761.
|
Up to 5 weeks
|
|
AUC from time zero to end of dosing interval AUC (0-tau)
大体时间:Up to 5 weeks
|
Plasma samples will be collected for the analysis AUC (0-tau) of GSK2248761.
|
Up to 5 weeks
|
|
Maximum concentration (Cmax) of GSK2248761
大体时间:Up to 5 weeks
|
Plasma samples will be collected for the analysis of Cmax of GSK2248761.
|
Up to 5 weeks
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Terminal half life (t1/2) of GSK2248761
大体时间:Up to 5 weeks
|
Plasma samples will be collected for the analysis of t1/2 of GSK2248761.
|
Up to 5 weeks
|
|
Lag time before observation of drug concentration (tlag) of GSK2248761
大体时间:Up to 5 weeks
|
Plasma samples will be collected for the analysis of tlag of GSK2248761.
|
Up to 5 weeks
|
|
Time to Cmax of GSK2248761
大体时间:Up to 5 weeks
|
Plasma samples will be collected for the analysis of Tmax of GSK2248761.
|
Up to 5 weeks
|
|
Percentage of AUC obtained by extrapolation (%AUCex) for GSK2248761
大体时间:Up to 5 weeks
|
Plasma samples will be collected for the analysis of %AUCex for GSK2248761.
|
Up to 5 weeks
|
|
Apparent clearance following oral dosing (CL/F) for GSK2248761
大体时间:Up to 5 weeks
|
Plasma samples will be collected for the analysis of CL/F for GSK2248761.
|
Up to 5 weeks
|
|
Number of participants with seious adverse events (SAEs) and non-serious adverse events (non-SAEs)
大体时间:Up to 5 weeks
|
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement.
|
Up to 5 weeks
|
|
Number of participants with concurrent medication
大体时间:Up to 5 weeks
|
Number of participants with concurrent medication will be summarized.
|
Up to 5 weeks
|
|
Number of participants with abnormal clinical laboratory parameters
大体时间:Up to 5 weeks
|
Blood samples will be collected for the analysis of clinical laboratory parameters.
|
Up to 5 weeks
|
|
Number of participants with abnormal electrocardiogram (ECG) values
大体时间:Up to 5 weeks
|
12-lead ECG will be obtained using an ECG machine.
Participants will be in supine or a semi-recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs are recorded.
|
Up to 5 weeks
|
|
Number of participants with abnormal vital signs
大体时间:Up to 5 weeks
|
Vital signs will be measured at indicated time points in semi-supine position after 5 minutes rest.
|
Up to 5 weeks
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2009年12月21日
初级完成 (实际的)
2010年3月11日
研究完成 (实际的)
2010年3月11日
研究注册日期
首次提交
2009年12月10日
首先提交符合 QC 标准的
2009年12月10日
首次发布 (估计)
2009年12月14日
研究记录更新
最后更新发布 (实际的)
2020年3月27日
上次提交的符合 QC 标准的更新
2020年3月25日
最后验证
2020年3月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.