The Effect of Rifampicin on the Plasma Pharmacokinetics of Emtricitabine (FTC) and Tenofovir Alafenamide Fumarate (TAF) and Intracellular Tenofovir-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by Ctrough.
研究概览
简要总结
The purpose of this study is to look at the levels of three HIV medications: Descovy®, Viread® and Rifadin® 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 28 days. Participants will take Descovy® on a first stage, a combination of Descovy® and Rifadin® on a second stage, and Viread® on a third stage. If the participants decide to take part, the duration of the study will be up to 85 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 28 to 36 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.
During the study, numerous blood samples will be taken which could cause inconvenience and distress for patients. Every effort will be made by study staff to minimise this. There are a lot of clinic visits during the study and three full days in the unit which may inconvenience patients. However, participants will be made aware of this both verbally and in the patient information sheet. Participants will also receive compensation for their time and travel expenses whilst participating in the trial. Participants or participants' partners who plan to become pregnant during the study will not be allowed to take part in the study. Further to this (if applicable), participants must use effective contraception for the duration of the study. Participants will have to adhere to other restrictions as detailed in the participant information sheet. These restrictions will be explained in full to all participants.
详细描述
To assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), emtricitabine, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC or TDF plus rifampicin in HIV negative healthy volunteers.
To assess the safety and tolerability of the co-administered drugs in HIV negative healthy volunteers. To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure. To investigate the impact of anti-retroviral drugs on platelet function in people living with HIV.
Among patients treated with antiretrovirals (ARVs), many will need to be treated for tuberculosis (TB) during their lifetime and Rifampicin (Rifadin) is the most commonly used treatment for tuberculosis. Every new ARV that becomes available for the treatment of HIV must be studied with rifampicin to understand whether it is safe to be used in patients on ARV treatment undergoing anti-TB treatment with rifampicin.
The total duration of the participant's involvement in the study will be 85 days plus a screening visit up to 28 days prior to the start of the study, and a follow up visit 27 to 35 days after the last blood measurement.
The participants will be asked to visit the clinic on 18 occasions, of which three visits involve staying in the unit for approximately 12 hours (day 28, 56 and 84). Blood samples will be taken from the participants throughout the study to measure the levels of Descovy, Viread and Rifadin in blood. Blood and urine will also be collected throughout the study for safety analysis. This is to ensure the participants are healthy to take part or to continue taking part in the study. The total amount of blood collected from each participant during the study will be approximately 590ml (approximately a pint).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Health Services Research
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 60 Years（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 60 years, inclusive
- •Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive (with weight ≥50kg).
- •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 4) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 3 months 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; (when this is in line with the preferred and usual lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception].
- •Any non-hormonal 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 4 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; 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 4 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); True 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 (When this is in line with the preferred and usual lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception].
- •Any non-hormonal intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see Appendix 4 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; Any contraception method must be used consistently, in accordance with the approved product label and for at least four weeks after discontinuation of IMP.
- •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 the study drugs and their components: tenofovir alafenamide fumarate, tenofovir disoproxil fumarate, emtricitabine or excipients, croscarmellose sodium, lactose monohydrate magnesium stearate (E572), microcrystalline cellulose (E460), starch pregelatinised, glycerol triacetate (E1518), hypromellose (E464), indigo carmine aluminium lake (E132), lactose monohydrate, titanium dioxide (E171), polyvinyl alcohol, macrogol 3350, talc, corn starch, magnesium stearate.
- •Current or recent (within three 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) or participation in a clinical study involving the donation of blood samples within three 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 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
Descovy® (TAF/FTC)
ATC Code J05AR17. Pharmaceutical form (use standard terms): Film-Coated Tablet Specific paediatric formulation?: No. Maximum duration of treatment of a subject according to the protocol: 56 days.
Maximum dose allowed 200mg/25mg per day. Total dose 200/25mg. Oral Use.
干预措施: Descovy® (TAF/FTC) (Drug)
Viread® (TDF)
ATC Code J05AF07. Pharmaceutical form (use standard terms): Film-Coated Tablet. Specific paediatric formulation?: No. Maximum duration of treatment of a subject according to the protocol 28 days.
Maximum dose allowed: 245mg per day. Total dose: 245mg. Oral Use.
干预措施: Viread® (TDF) (Drug)
Rifadin® (Rifampicin)
ATC Code J0AB02 Pharmaceutical form (use standard terms): Capsule, Hard. Specific paediatric formulation?: No. Maximum duration of treatment of a subject according to the protocol 28 days.
Maximum dose allowed: 600mg per day. Total dose: 600mg. Oral Use.
干预措施: Rifadin® (Rifampicin) (Drug)
结局指标
主要结局
Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by Ctrough.
时间窗: 12 Weeks
Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, in HIV negative healthy volunteers, as measured by Ctrough. Trough concentration (Ctrough) is defined as the concentration at 24 hours after the observed drug dose.
Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by Cmax.
时间窗: 12 weeks
Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin in HIV negative healthy volunteers, as measured by Cmax. Cmax is defined as the maximum observed plasma concentration.
Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by t1/2
时间窗: 12 weeks
Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin in HIV negative healthy volunteers, as measured by t1/2. t1/2 = Elimination half-life
Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by Tmax
时间窗: 12 weeks
Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin in HIV negative healthy volunteers, as measured by Tmax. Tmax = time point at Cmax
Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by total drug exposure
时间窗: 12 weeks
Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin in HIV negative healthy volunteers, as measured by total drug exposure. Total drug exposure is expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h)
次要结局
- Assess the safety and tolerability of the studied drugs when co-administered to HIV negative healthy volunteers, assessed by The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events(12 Weeks)
- Exploratory: Investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by Peak plasma concentration (Cmax)(12 Weeks)
- Exploratory: Investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by trough concentration (Ctrough)(12 Weeks)
- Exploratory: Investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by by Area under the plasma concentration versus time curve (AUC)(12 Weeks)
- Exploratory: the impact of antiretroviral drugs on platelet function(12 Weeks)