Pharmacokinetics, Safety and Acceptability of a Solid Paediatric Fixed-dose Combination of Darunavir/Ritonavir (DRV/r) 120/20 mg for Children Living With HIV
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 50
- 试验地点
- 8
- 主要终点
- Pharmacokinetics Darunavir
研究概览
简要总结
The UNIVERSAL2 study is a research project designed to evaluate a newly developed formulation of an approved drug for children living with HIV aged over 3 years and weighing between 10 and 25 kg. The aim of UNIVERSAL2 is to determine the right dosage of this new formulation.
详细描述
The UNIVERSAL2 study is a research project designed to evaluate a newly developed formulation of an approved drug for children living with HIV aged over 3 years and weighing between 10 and 25 kg. The aim of UNIVERSAL2 is to determine the right dosage of this new formulation.
It is a combination of two anti-HIV medicines called darunavir (DRV) and ritonavir (RTV). The DRV/RTV combination is well known and has been used for a long time in adults and children to treat HIV infection but there is no combined pediatric formulation that has been adapted to the needs of children ("child friendly" formulation).
The new combination has been developed in the form of fixed-dose combination tablets with a dose of 120 mg of DRV and 20 mg of RTV (DRV/RTV 120/20) in each tablet. Depending on their weight and the need to take the medication once or twice a day, children may receive 2, 3 or 4 DRV/RTV 120/20 tablets at any given time.
The aim of UNIVERSAL2 is to determine the correct dosage and to assess the safety and acceptability of the new drug for children living with HIV.
The study will focus on two groups of children.
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
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Confirmed HIV-1 infection
- •Aged ≥ 3 years
- •With unsuppressed viral load (HIV-1 RNA viral load > 1000 c/mL) on ART-regimen and eligible to switch to new DRV/r 120/20 mg-based regimen per investigator's judgement
- •Able to swallow the 120/20 mg DRV/r tablets
- •Willing to receive the 120/20 mg DRV/r tablets
- •Parents or guardians, and children where appropriate, willing and able to give informed consent and to adhere to the protocol
- •Cohort-specific inclusion criteria:
- •Have 1 or 2 DRV resistance-associated mutations (RAMs)*
- •Weigh 10 to <25 kg at screening
- •Have no DRV RAMs*
- •Weigh 10 to <20 kg at screening. *DRV RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V
排除标准
- •Presence of >2 darunavir RAMs*
- •Failure of protease genotypic resistance testing at baseline, except if treatment history indicates that it is very unlikely
- •Resistance to all NRTI available in the country or impossibility to define an OBT
- •Intercurrent illness (enrolment can take place after the illness resolves)
- •Creatinine ≥ 1.8 Upper Limit of Normal (ULN) or ALT ≥ 5 ULN or (ALT ≥ 3 ULN and bilirubin ≥2 ULN) at screening.
- •Severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •History or presence of known allergy or other contraindication to DRV/r or their components as described in the Summary of Product Characteristics (SmPC)
- •Concomitant medications that may interact with the current antiretroviral treatment, in particular TB drugs (i.e: rifampicin, rifabutin, rifapentine, …).
研究组 & 干预措施
Cohort A Twice daily
DRV/r twice daily (BID): 30 children with 1 or 2 DRV RAM* weighing 10 to <25 kg (10 per weight band: 10-13.9kg, 14-19.9kg, 20-24.9kg)
干预措施: DRV/r FDC (120/20mg) (Drug)
Cohort B Once daily
DRV/r once daily (OD): 20 children with no DRV RAM* weighing 10 to <20 kg (10 per weight band: 10-13.9kg, 14-19.9kg)
*DRV RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V
干预措施: DRV/r FDC (120/20mg) (Drug)
结局指标
主要结局
Pharmacokinetics Darunavir
时间窗: From enrollment to the end of treatment at 24 weeks
area under the concentration-time curve (AUC0-12) (Cohort A)
Safety events
时间窗: From enrollment to the end of treatment at 24 weeks
serious adverse events (SAEs)
次要结局
- Pharmacokinetics Ritonavir(From enrollment to the end of treatment at 24 weeks)
- Acceptability(From enrollment to the end of treatment at 24 weeks)
- Efficacy of treatment(From enrollment to the end of treatment at 24 weeks)