Study on PhArmacokinetics of First liNe Antiretrovirals in Healthy Breastfeeding Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio
研究概览
简要总结
No to little data exists on penetration of antiretroviral drugs in breastmilk. Too high concentrations may lead to infant toxicity and too low concentrations may lead to development of resistance in case the infant inadvertently becomes infected with the virus.
The aim of this trial is to determine the concentration of currently often used ARV (doravirine, raltegravir, bictegravir, tenofovir alafenamide, emtricitabine) in breast milk after administration of a single dose Study design: This is a single centre, single dose, open label, pharmacokinetic study in healthy volunteers.
Study population: Adult, healthy volunteers at the end of their breastfeeding period Intervention: Administration of one dose of either doravirine (DOR) 100mg, raltegravir (RAL) 1200mg or a combination of tenofovir alafenamide 25mg, emtricitabine 200mg and bictegravir 50mg (BIC/FTC/TAF).
Main study parameters/endpoints: Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio.
详细描述
Rationale: Although current guidelines advise against breastfeeding while using antiretrovirals in people living with HIV, some women choose to breastfeed because advantages of breastfeeding may exceed the possible risk of HIV transmission to the newborn. However, no sound recommendation can be made on which antiretrovirals are most suitable during breastfeeding, because no to little data on penetration of these drugs in breastmilk exist. Too high concentrations may lead to infant toxicity and too low concentrations may lead to development of resistance in case the infant inadvertently becomes infected with the virus.
Objective: to determine the concentration of currently often used ARV (doravirine, raltegravir, bictegravir, tenofovir alafenamide, emtricitabine) in breast milk after administration of a single dose Study design: This is a single centre, single dose, open label, pharmacokinetic study in healthy volunteers.
Study population: Adult, healthy volunteers at the end of their breastfeeding period Intervention: Administration of one dose of either doravirine (DOR) 100mg, raltegravir (RAL) 1200mg or a combination of tenofovir alafenamide 25mg, emtricitabine 200mg and bictegravir 50mg (BIC/FTC/TAF).
Main study parameters/endpoints: Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Subjects will not directly benefit from this study, but will contribute to knowledge on breastmilk transfer of ARV and possibly enable people living with HIV to make an informed decision on breastfeeding while using these medications.
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 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •At least 18 years of age at the moment of screening
- •At least 10 days post partum
- •At the end of breastfeeding period; subject is able to produce breastmilk at least two times a day and is no longer feeding infant at start of study
- •Able and willing to sign an informed consent
排除标准
- •Relevant co-medication or comorbidity that might interfere with drug absorption, distribution, metabolism or excretion
- •Inability to take drugs according to the instructions (i.e. with food)
- •Presence of positive HIV screening or HIV RNA
- •Presence of HBsAg or HBcAg without anti-HBs
- •Presence of grade III/IV anaemia (i.e. Hb <4.6 mmol/L or <7.4 g/dL).
- •Presence of hereditary forms of severe galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
研究组 & 干预措施
Doravirine
1 single dose of 100mg doravirine taken orally
干预措施: Doravirine 100Mg Tab (Drug)
Biktarvy
1 single dose of 25/200/50mg taken orally
干预措施: Biktarvy 50/200/25 Tab (Drug)
结局指标
主要结局
Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio
时间窗: 24hours after ingestion of study drug
M:P ratio
M:P Ratio
时间窗: 24hours after ingestion of study drug
Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio
次要结局
- AUC over a dosing interval(24hours after ingestion of study drug)
- Clearance of study drugs(24hours after ingestion of study drug)
- Apparent volume of distribution(24hours after ingestion of study drug)
- Peak plasma concentration(Within 24 hours after ingestion of study drug)
- Concentration at the end of dosing interval(24hours after ingestion of study drug)
- Half life(24hours after ingestion of study drug)
- AUCtau(24hours after ingestion of study drug)
- Cmax(Within 24 hours after ingestion of study drug)
- Ctrough(24hours after ingestion of study drug)
- Clearance of Study Drugs(24hours after ingestion of study drug)
- Apparent Volume of Distribution(24hours after ingestion of study drug)
- Half Life(24hours after ingestion of study drug)