Effects of Ledipasvir/Sofosbuvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) in Patients With HIV.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks
研究概览
简要总结
This study will evaluate the effect of ledipasvir/sofosbuvir (LDV/SOF) treatment on the pharmacokinetics (PK) and renal safety of tenofovir in the form of tenofovir alafenamide (TAF). Subjects living with human immunodeficiency virus (HIV) who are receiving tenofovir-based antiretroviral therapy (in the form of tenofovir disoproxil fumarate [TDF]), and are also taking a ritonavir- or cobicistat-boosted protease inhibitor will be invited to participate.
The study will consist of five visits: a screening visit, three abbreviated 4-hour pharmacokinetic visits, and one end-of-study follow-up visit.
Subjects will also be asked to use a Wisepill device, which will track medication adherence throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between 18-70 years of age
- •Have been taking TDF and a ritonavir- or cobicistat-boosted protease inhibitor as part of standard care for treatment of HIV
排除标准
- •eGFR < 30 mL/min
- •Pregnant or planning pregnancy
- •Breastfeeding
- •Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes
- •Signs or symptoms of decompensated liver disease
- •Hepatitis B infection
- •Medications that may cause unwanted drug interactions with ledipasvir/sofosbuvir or emtricitabine/tenofovir alafenamide
- •Unwillingness or inability to comply with study procedures
- •Chronic hepatitis C infection
研究组 & 干预措施
TAF with a boosted PI and LDV/SOF
Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment.
Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks.
After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks.
Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study.
干预措施: TDF with a boosted protease inhibitor (Drug)
TAF with a boosted PI and LDV/SOF
Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment.
Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks.
After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks.
Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study.
干预措施: TAF with a boosted protease inhibitor (Drug)
TAF with a boosted PI and LDV/SOF
Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment.
Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks.
After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks.
Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study.
干预措施: TAF with a boosted protease inhibitor and LDV/SOF (Drug)
结局指标
主要结局
Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks
时间窗: 12 weeks and 24 weeks and 28 weeks
Compare plasma tenofovir AUC0-24 between TAF with boosted PI vs. TDF with boosted PI (Phase 2 vs. 1), and between TAF with boosted PI and LDV/SOF vs. TDF with boosted PI (Phase 3 vs. 1)
Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) at 24 and 28 Weeks
时间窗: 12 weeks, and 24 weeks and 28 weeks
Compare tenofovir-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1).
次要结局
- Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS)(12 weeks and 24 and 28 weeks)
- Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: eGFR(12 weeks, 24 weeks, and 28 weeks)
- Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: UPCR(12 weeks, 24 weeks, and 28 weeks)
- Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: B2M/Cr Ratio, and RBP/Cr Ratio(12 weeks, 24 weeks, and 28 weeks)