Steady-state Pharmacokinetics of Atazanavir/Cobicistat and Darunavir/Cobicistat Once Daily Over 72 Hours in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by t1/2
研究概览
简要总结
The purpose of this study is to look at the levels of three HIV medications: atazanavir, darunavir and cobicistat in the blood after drug intake has been stopped, in order to understand how long these drugs persist in the blood. The study will specifically look at blood levels of these three drugs after taking them every day for 10 days. Participants will take Evotaz (atazanavir and cobicistat) on a first stage and Rezolsta (darunavir and cobicistat) on a second stage.
If the participants decide to take part, the duration of the study will be up to 33 days plus a screening visit which will take place up to 28 days prior to the start of the study, and a follow up visit, which takes place 7 to 14 days after the last dose of study medication. This study is not randomised which means that all participants will receive all study medications in the same order.
The participant and the study doctor will know which study medications the participant is taking at all times during the study.
详细描述
Protocol Number: SSAT067
EudraCT Number: 2015-002956-28
Name of Investigational Product: Evotaz®, Rezolsta®
Name of active ingredients: Atazanavir, darunavir and cobicistat
Study title: Steady-state Pharmacokinetics of Atazanavir/Cobicistat and Darunavir/Cobicistat Once Daily Over 72 Hours in Healthy Volunteers
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •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
- •ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.
- •Women of childbearing potential (WOCBP - definition in Appendix 5) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 4 weeks after the study
- •A female may be eligible to enter and participate in the study if she:
- •is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
- •is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
- •Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications;
- •Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
- •Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see protocol appendix 5 for an example listing of approved IUDs);
- •Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject;
- •Approved hormonal contraception (see protocol appendix 5 for a listing of examples of approved hormonal contraception) plus male condom;
- •Any other method with published data showing that the expected failure rate is <1% per year.
- •Any contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of IP.
- •Men who have partners who are women of childbearing potential (WOCBP - definition in Appendix 5) must be using an adequate method of contraception to avoid pregnancy in their partner throughout the study and for a period of at least 4 weeks after the study (see inclusion criteria 6)
- •Willing to consent to their personal details being entered onto the TOPS database
- •Willing to provide proof of identity by photographic ID at screen and any subsequent visit
- •Registered with a GP in the UK
排除标准
- •Any clinically 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 surface antigen or C antibody
- •Positive blood screen for HIV-1 or 2 by antibody/antigen assay
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •History or presence of allergy to darunavir, atazanavir cobicistat or excipients (sodium methyl parahydroxybenzoate, lactulose, Hypromellose Colloidal silicon dioxide, Silicified microcrystalline cellulose Crospovidone, Magnesium stearate, Polyvinyl alcohol- partially hydrolysed, Macrogol 3350,Titanium dioxide, Talc, Iron oxide red, Iron oxide black, Lactose monohydrate, Magnesium stearate, Gelatine Yellow iron oxide, Indigocarmin (E132), White ink, Shellac,Titanium dioxide (E171), Ammonium hydroxide, Propylene glycol , Simethicone, Hypromellose, Polyvinyl alcohol- partially hydrolysed, Macrogol 3350)
- •Current or recent (within 3 months) gastrointestinal disease
- •Known intolerance of lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
- •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) or participation in a clinical study involving the donation of blood samples within 3 months of first dose of study drug
- •Use of any other drugs (unless approved by the Investigator), 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 4 weeks after the end of the treatment period
研究组 & 干预措施
Evotaz®, washout, then Rezolsta®
All participants will be administered Evotaz®) (atazanavir 300mg + cobicistat 150mg) once daily for 10 days, undergo a ten-day wash out period and then take Rezolsta® (darunavir 800mg + cobicistat 150mg) once daily for 10 days.
干预措施: Evotaz (Drug)
Evotaz®, washout, then Rezolsta®
All participants will be administered Evotaz®) (atazanavir 300mg + cobicistat 150mg) once daily for 10 days, undergo a ten-day wash out period and then take Rezolsta® (darunavir 800mg + cobicistat 150mg) once daily for 10 days.
干预措施: Rezolsta (Drug)
结局指标
主要结局
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by t1/2
时间窗: Days 10 and 30
t1/2 = Elimination half-life
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by Tmax
时间窗: Days 10 and 30
Tmax = time point at Cmax
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by Cmax
时间窗: Days 10 and 30
Cmax defined as the maximum observed plasma concentration.
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by total drug exposure
时间窗: Days 10 and 30
Total drug exposure is expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h) and 0-72 hours (AUC0-72h)
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers as measured by Ctrough
时间窗: Days 10 and 30
Trough concentration (Ctrough) is defined as the concentration at 24 hours after the observed drug dose
次要结局
- To assess the inter subject variability in atazanavir, darunavir and cobicistat plasma concentrations over 72 hours(Days 10 and 30)
- To assess the safety and tolerability of the studied drugs over 10 days in HIV negative healthy volunteers, assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events.(Screening (day -28) to follow-up visit (day 41-54))
- To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by Area under the plasma concentration versus time curve (AUC)(Day 1)
- To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by trough concentration (Ctrough)(Day 1)
- To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by Peak plasma concentration (Cmax)(Day 1)