双剂量多替拉韦与利福喷汀联合治疗 HIV 相关结核病的药代动力学和安全性
A5406 假设每天服用两次 50 毫克多替拉韦 (DTG) 与 1200 毫克利福喷汀 (RPT) 一起用于 HIV 相关结核病时，将提供足够的暴露以维持病毒抑制。
研究概览
地位
完全的
条件
详细说明
这是一项开放标签、单臂、II 期、多中心 PK 研究，旨在研究每日 RPT 1200 mg 对 HIV 相关结核病参与者暴露于 DTG 的影响。
将在 DS TB 诊断前后招募目前未接受 ART 的新诊断 DS-TB 感染 HIV 的成人。
在研究开始时，将启动 2HPZM/2HPM 方案进行抗结核（抗结核）治疗并持续 17 周。
研究类型
介入性
注册 (实际的)
30
阶段
- 阶段2
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
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Cape Town, Western Cape
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Mowbray、Cape Town, Western Cape、南非、7700
- University of Cape Town Lung Institute (UCTLI) CRS (Site # 31792)
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Durban
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Wentworth、Durban、南非、4052
- Durban International CRS (Site # 11201)
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Western Cape
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Worcester、Western Cape、南非、6850
- South African Tuberculosis Vaccine Initiative (SATVI) CRS (Site # 31793)
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Bangkok、泰国、10330
- Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (Site # 31802)
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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
14年 及以上 (成人、年长者)
接受健康志愿者
不
描述
纳入标准：
- 进入研究时年满 18 岁的个人。
- 体重≥40 公斤。
- 体重指数 (BMI) >18.5 公斤/平方米。
- 参与者或法定监护人/代表提供知情同意的能力和意愿。
- HIV-1 状态的文档。
- CD4+ 细胞计数≥100 个细胞/mm3 在进入研究前 30 天内在任何获得 IQA 认证的网络批准的非美国实验室获得。
- 在结核病诊断前连续 12 周未接受过 ART 治疗或未接受过 ART 治疗。
- 在开始 TB 治疗后 6 周开始基于 DTG 的 ART 的意愿和资格，窗口为 ±1 周，并且无意在研究期间改变 ART。
- 肺结核的文件。
- 愿意开始 DS-TB 的 2HPZM/2HPM 治疗。
在进入研究前 30 天内获得的以下实验室值：
- 中性粒细胞绝对计数 (ANC) >750 个细胞/mm3
- 血红蛋白≥7.4 g/dL
- 血小板计数≥50,000/mm3
- 天冬氨酸氨基转移酶 (AST)（血清谷氨酸草酰乙酸转氨酶 [SGOT]）<2.5 X 正常值上限 (ULN)
- 丙氨酸转氨酶 (ALT)（血清谷丙转氨酶 [SGPT]）<2.5 x ULN
- 总胆红素≤1.5 x ULN
- 肌酐 <1.3 x ULN
- 对于可能怀孕的参与者，在入场前 30 天内和入场前 48 小时内筛查时血清或尿液妊娠试验呈阴性。
- 可以怀孕的参与者必须同意不参与受孕过程，如果参与可能导致怀孕的性活动，则必须同意使用一种可靠的非激素避孕方法。
- 入职前 30 天内 Karnofsky 表现评分≥50 的文件。
排除标准：
- 母乳喂养、怀孕或计划怀孕。
- 已知过敏/敏感性或对研究药物成分或其制剂的任何超敏反应。
- 现场调查员认为会干扰对研究要求的依从性的药物或酒精使用或依赖。
- 要求持续使用已知与 DTG 或 RPT 有显着药物相互作用的药物。
- 已知有急性间歇性卟啉症病史。
- 既往接受过活动性结核病治疗。
- 超过 5 天的针对活动性结核病的治疗在进入研究之前的当前结核病发作。
- 在进入研究时，从已知对 RIF 或 INH 具有耐药性的当前或先前治疗事件中分离出结核分枝杆菌的文件。
- 已知的 QT 间期延长综合征病史。
- 已知肝硬化、失代偿性肝病病史（腹水、肝性脑病或食管静脉曲张）。
- 根据现场调查员的意见，在进入研究后 3 个月内记录严重机会性感染。
- 筛选时严重肺外结核病（例如脑膜炎、骨髓炎、播散性结核病）的记录。
- 筛查时患有急性痛风。
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：不适用
- 介入模型：单组作业
- 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：Adults with HIV and newly diagnosed DS-TB not currently on ART
Participants received daily rifapentine-moxifloxacin plus isoniazid and pyrazinamide for 8 weeks followed by daily rifapentine-moxifloxacin plus isoniazid for 9 weeks (referred to as 2HPZM/2HPM) for anti-TB therapy at study entry. DTG-based ART at 50 mg BID was started after 6 weeks of TB therapy and continued for 2 weeks after completion of TB therapy. Two weeks after completion of TB therapy DTG was reduced to standard dose 50 mg QD. |
从结核病治疗完成后两周到研究结束（第 48 周），口服 DTG 50 mg QD 加 TDF/3TC。
Dolutegravir (DTG) 50 mg orally BID (~12 hours apart) plus TDF/3TC, from study week 6 until 2 weeks after completion of TB treatment: Morning dose DTG 50 mg QD plus TDF/3TC from study-supplied ART regimen.
Evening dose: DTG 50 mg orally QD from study-supplied source.
Daily regimen of rifapentine 1200mg, moxifloxacin 400mg, isoniazid 300mg, and pyrazinamide at standard doses adjusted for body weight from study entry through study week 8.
Daily regimen of rifapentine 1200mg, moxifloxacin 400mg, and isoniazid 300mg from study week 8 through study week 17.
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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 |
|---|---|---|
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Model-simulated 5th Percentile and Corresponding 95% Confidence Interval of DTG Cmin at 50 mg BID When Co-administered With Daily RPT 1200 mg Plus HZM
大体时间：Measured at week 8 and week 21. Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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Model-simulated 5th percentile and corresponding 95% confidence interval of dolutegravir (DTG) minimum concentrations (Cmin) at 50 mg BID (twice daily) when co-administered with daily rifapentine (RPT) 1200 mg plus HZM (isoniazid, pyrazinamide, and ethambutol).
Pharmacokinetic parameters were estimated using nonlinear mixed-effects modelling (FOCE-I).
The final model was used to simulate 10000 individuals, incorporating parameter uncertainty.
Covariates included fat-free mass on disposition parameters, rifapentine on clearance and bioavailability, and baseline unconjugated bilirubin on clearance.
Measurements were taken at steady state, which was assumed to be achieved after at least 5 half-lives.
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Measured at week 8 and week 21. Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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DTG Minimum Concentration (Cmin)
大体时间：Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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Primary pharmacokinetic (PK) parameters were estimated using nonlinear mixed-effects modelling.
Secondary model-predicted parameters were derived post-hoc via simulations in R using the mrgsolve package.
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Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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DTG Maximum Concentration (Cmax)
大体时间：Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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Primary pharmacokinetic parameters were estimated using nonlinear mixed-effects modelling.
Secondary model-predicted parameters were derived post-hoc via simulations in R using the mrgsolve package.
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Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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DTG Area Under the Concentration-time Curve (AUC0-24)
大体时间：Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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Primary pharmacokinetic parameters were estimated using nonlinear mixed-effects modelling.
Secondary model-predicted parameters were derived post-hoc via simulations in R using the mrgsolve package.
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Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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DTG Clearance
大体时间：Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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Primary pharmacokinetic parameters were estimated using nonlinear mixed-effects modelling.
Secondary model-predicted parameters were derived post-hoc via simulations in R using the mrgsolve package.
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Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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DTG Terminal Half Life
大体时间：Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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Primary pharmacokinetic parameters were estimated using nonlinear mixed-effects modelling.
Secondary model-predicted parameters were derived post-hoc via simulations in R using the mrgsolve package.
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Measured at week 8 and week 21; Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing.
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Percent of Participants Who Experienced Grade 3 or Higher Adverse Events (AE)
大体时间：Week 6 through week 17
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The time frame specifically encompasses the time period the participants were on both ART and TB treatment which was scheduled to occur between study weeks 6 and 17.
Adverse events were graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death.
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Week 6 through week 17
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Percent of Participants Who Experienced Rifamycin Hypersensitivity
大体时间：Week 6 through week 17
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The time frame specifically encompasses the time period the participants were on both ART and TB treatment which was scheduled to occur between study weeks 6 and 17.
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Week 6 through week 17
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Percent of Participants Who Experienced Drug-induced Liver Injury
大体时间：Week 6 through week 17
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Drug-induced liver injury was defined as alanine animotransferase (ALT) ≥3xULN (upper limit of normal) with symptoms/jaundice or ALT ≥5xULN. The time frame specifically encompasses the time period the participants were on both ART and TB treatment which was scheduled to occur between study weeks 6 and 17. |
Week 6 through week 17
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Percent of Participants Who Prematurely Discontinued Study Treatment
大体时间：Week 6 through week 17
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The time frame specifically encompasses the time period the participants were on both ART and TB treatment which was scheduled to occur between study weeks 6 and 17.
Study treatment discontinuation included discontinuing either ART, TB treatment, or both.
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Week 6 through week 17
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Percent of Participants With Viral Suppression
大体时间：Weeks 10, 14, 21, and 30
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Viral suppression is defined as HIV-1 RNA below 50 copies/mL.
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Weeks 10, 14, 21, and 30
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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。
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)
2024年2月13日
初级完成 (实际的)
2025年5月7日
研究完成 (实际的)
2025年11月12日
研究注册日期
首次提交
2022年11月18日
首先提交符合 QC 标准的
2022年11月18日
首次发布 (实际的)
2022年11月30日
研究记录更新
最后更新发布 (实际的)
2026年7月20日
上次提交的符合 QC 标准的更新
2026年7月16日
最后验证
2026年7月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- A5406
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
是的
IPD 计划说明
在去标识化后，作为出版物结果基础的个人参与者数据。
IPD 共享时间框架
从出版后 3 个月开始，在 NIH 艾滋病临床试验小组资助期间可用。
IPD 共享访问标准
- 和谁一起？ 为使用经 AIDS 临床试验组批准的数据提供方法学合理建议的研究人员。
- 用于什么类型的分析？ 实现艾滋病临床试验小组批准的提案中的目标。
- 将通过什么机制提供数据？ 研究人员可以使用 AIDS 临床试验组“数据请求”表格提交访问数据的请求：https://actgnetwork.org/submit-a-proposal/。 获得批准的提案的研究人员在收到数据之前需要签署一份艾滋病临床试验组数据使用协议。
IPD 共享支持信息类型
- 研究方案
- 树液
药物和器械信息、研究文件
研究美国 FDA 监管的药品
是的
研究美国 FDA 监管的设备产品
不
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.