Doravirine Dose Optimisation in Pregnancy
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Cmax of doravirine in pregnant women
研究概览
简要总结
A randomised, open label, controlled PK standard of care vs doravirine plus 2 nucleoside reverse transcriptase inhibitors backbone in pregnant women initiating combination antiretroviral therapy in the second trimester of pregnancy.
详细描述
Women diagnosed HIV positive in the second trimester of pregnancy in South Africa will be enrolled and randomised 1:1 to receive standard of care or doravirine plus 2 NRTI backbone. Participants will receive study treatment until delivery and up to 28 weeks postpartum, with a maximum total of 14 months of study treatment. Given the high prevalence of NNRTI resistance, alternative ARV treatment options are essential. Doravirine is licenced for the treatment of HIV-1 in adults in North America and Europe. Whilst the efficacy and safety of doravirine has been established in non-pregnant adults, there are no adequate human data available to establish whether DOR poses a risk to pregnancy outcomes. It is important to have data on the safety and pharmacokinetics of the drug during pregnancy and in particularly the third trimester of pregnancy in order to support its use. The hypothesis for this study is that pregnancy influences the pharmacokinetics of doravirine when initiated in the second trimester.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women ≥ 18 years old
- •Ability to give informed consent prior to participation
- •Willing and able to comply with all study requirements
- •HIV positive
- •Pregnant (initiating cART ≥ 12 weeks and < 26 weeks gestation)
- •Intention to breastfeed postpartum
排除标准
- •Received any cART in preceding 6 months
- •Chronic hepatitis B (HBV) infection with clinical evidence of transaminitis
- •Elevations in serum levels of alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN) or ALT > 3xULN and bilirubin >2xULN (with > 35 % direct bilirubin)
- •Previous documented failure of an NNRTI-containing cART regimen
- •Previous history of hypersensitivity to any ARV
- •Concomitant medication which are inducers of SoC and DOR metabolism (e.g. rifampicin, anti-epileptic agents, rifabutin, St John's Wort, mitotane, enzalutamide, lumacaftor). Contraindicated medications can be found on Liverpool Drug Interactions website (hiv-druginteractions.org)
- •Participants with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption cannot take DOR as the tablet contains lactose monohydrate
- •Clinical depression or clinical judgment suggests increased risk of suicidality
研究组 & 干预措施
Delstrigo
doravirine/lamivudine/tenofovir disoproxil 100 mg/ 300 mg/ 245 mg film coated tablets, dosed 1 tablet once daily for the duration of the study
干预措施: Doravirine (Drug)
Standard of care
dolutegravir/lamivudine/tenofovir disoproxil 50 mg/300 mg/245 mg film coated tablets, dosed 1 tablet once daily for the duration of the study
干预措施: Dolutegravir (Drug)
结局指标
主要结局
Cmax of doravirine in pregnant women
时间窗: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Pharmacokinetic parameters of doravirine in pregnancy - Cmax
CL/F of doravirine in pregnant women
时间窗: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Pharmacokinetic parameters of doravirine in pregnancy - CL/F
AUC of doravirine in pregnant women
时间窗: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Pharmacokinetic parameters of doravirine in pregnancy - AUC
Cmin of doravirine in pregnant women
时间窗: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Pharmacokinetic parameters of doravirine in pregnancy - Cmin
次要结局
- To assess the number of treatment related adverse events by DAIDS v2.1(Until study completion, a maximum of 13 months)
- To determine the concentration of doravirine in breastmilk, in breastfed infants, in genital tract, cord blood(24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum)
- To assess maternal viral load responses(Delivery and 6 months postpartum)
- To determine infant transmissions in the first 6 months of life using HIV viral load(Delivery until 6 months postpartum)
- To assess the prevalence or emergence of HIV drug resistance by determining HIV mutations(Until study completion, a maximum of 13 months)