Pharmacokinetics, Safety and Efficacy of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen in Patients With Intolerance and/or Resistance to NRTIs, NNRTIs and RTV: A Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 4
- 主要终点
- Area under the plasma concentration versus time curve (AUC) of atazanavir, dolutegravir and lamivudine
研究概览
简要总结
During the past years the treatment of HIV-1 infection has transformed towards chronic treatment. Patients are being treated with antiretroviral drugs for many years and become older. The risk of developing side-effects due to long term antiretroviral therapy is therefore more and more likely. New alternative once-daily maintenance regimes are needed for those who are extensively pre-treated and experience side-effects or toxicity on standard treatment combinations. A possible once-daily, fully active maintenance regimen is the combination of atazanavir (unboosted), dolutegravir and lamivudine (PRADAII regimen). This combination is expected to be a safe, once-daily maintenance regimen with a favorable side-effect profile. The combination suits patients with intolerance and/or resistance to NRTIs, NNRTIs and ritonavir, who have a suppressed viral load. However, for this new combination the pharmacokinetic profile is unknown and there are no data on short-term and long-term safety and efficacy. This study wille therefore asses the pharmacokinetics, safety and efficacy in a small number of HIV-1 infected patients.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
- •Subject is in need for a switch in maintenance regimen due to adverse effects, toxicities, simplification and/or resistance.
- •Subject is at least 18 years of age at the day of screening.
- •Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- •HIV-1 RNA < 40 copies/mL for at least 6 months on antiretroviral therapy prior to inclusion.
- •Subject has no documented resistance mutations to PIs, INSTIs or lamivudine.
排除标准
- •Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- •Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- •Inability to understand the nature and extent of the trial and the procedures required.
- •Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
- •Abnormal serum transaminases determined as levels being > 5 times upper limit of normal.
- •Renal failure determined as an estimated Glomerular Filtration Rate (eGFR) < 50 ml/min (MDRD-based).
- •Concomitant use of medications that interfere with atazanavir, dolutegravir or lamivudine pharmacokinetics: oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John's wort, rifampicin, clarithromycin, H2 receptor antagonists, proton pump inhibitors, irinotecan, midazolam, triazolam, buprenorphine, aprepitant, modafinil, imatinib, co-trimoxazole, other antiretroviral drugs.
- •Concomitant use of medications that are contraindicated for use with atazanavir, dolutegravir or lamivudine: alfuzosin, dofetilide, pimozide, quetiapine, quinidine, bepridil, simvastatin, atorvastatin, lovastatin, sildenafil (as for use in pulmonary arterial hypertension), cladribine.
- •Active hepatobiliary or hepatic disease (including chronic hepatitis B or C infection).
- •Alcohol abuse.
研究组 & 干预措施
PRADAII regimen
Use of PRADAII regimen during 12 weeks. This regimen consists of atazanavir 400 mg QD, dolutegravir 50 mg QD, lamivudine 300 mg QD.
干预措施: Atazanavir (Drug)
PRADAII regimen
Use of PRADAII regimen during 12 weeks. This regimen consists of atazanavir 400 mg QD, dolutegravir 50 mg QD, lamivudine 300 mg QD.
干预措施: Dolutegravir (Drug)
PRADAII regimen
Use of PRADAII regimen during 12 weeks. This regimen consists of atazanavir 400 mg QD, dolutegravir 50 mg QD, lamivudine 300 mg QD.
干预措施: Lamivudine (Drug)
结局指标
主要结局
Area under the plasma concentration versus time curve (AUC) of atazanavir, dolutegravir and lamivudine
时间窗: week 2
Pharmacokinetic parameters of atazanavir, dolutegravir and lamivudine
次要结局
- efficacy (viral load)(week 2, 6 and 12)
- number of adverse events(week 2, 6 and 12)