A Multi-part, Phase 1, First-Time-in-Human Study to Investigate Safety, Tolerability, and PK of VH4770359 in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Number of participants with Grade 3 and Grade 4 adverse events (AEs)
研究概览
简要总结
VH4770359 (also known as GSK4770359) is an antiretroviral compound. This first-in-human study aims to evaluate the safety, tolerability, and pharmacokinetics (PK) of orally administered VH4770359 in healthy participants. The findings from this study will support the design of future clinical studies of VH4770359 in people living with HIV.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blind.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 to 55 years old
- •BMI 18.5-37.0 kg/m2
- •Male participants must adhere to contraception requirements or abstinence, and female participants must not be pregnant/breastfeeding and be of non-childbearing potential.
排除标准
- •Participants with significant medical history that could alter drug pharmacokinetics, pose a risk, or interfere with conduct.
- •Has exclusionary psychiatric, hepatic, cardiovascular, gastrointestinal, respiratory, endocrine, neurological, hematological, or renal condition, or exclusionary malignancy.
- •A positive test(s) for Hepatitis B surface antigen (HBsAg) and/or anti-HBc, hepatitis C antibodies, or human immunodeficiency virus (HIV).
- •A history of or ongoing high-risk behaviors for HIV acquisition.
- •Use of prohibited medications.
- •Exclusionary allergies or sensitivities.
- •Regular use of alcohol, drugs of abuse, tobacco, or nicotine products.
- •Exclusionary prior or concurrent clinical study participation.
研究组 & 干预措施
Part A: VH4770359 SAD group
Healthy participants will receive a single dose of VH4770359 on Day 1. Up to 7 cohorts will receive single ascending doses (SAD).
干预措施: VH4770359 (Drug)
Part A: Placebo SAD group
Healthy participants will receive a single dose of Placebo on Day 1.
干预措施: Placebo (Drug)
Part B: VH4770359 MAD group
Healthy participants will receive 14 daily repeat doses of VH4770359 from Day 1 to Day 14. Up to 4 cohorts will receive multiple ascending doses (MAD).
干预措施: VH4770359 (Drug)
Part B: VH4770359 MAD Drug-Drug Interaction (DDI) group
Healthy participants will receive 14 daily repeat doses of VH4770359 from Day 1 to Day 14. Participants will also receive 2 mg Midazolam on Days -1, Day 1 and Day 14.
干预措施: VH4770359 (Drug)
Part B: Placebo MAD group
Healthy participants will receive 14 daily repeat doses of Placebo from Day 1 to Day 14.
干预措施: Placebo (Drug)
Part B: Placebo MAD DDI group
Healthy participants will receive 14 daily repeat doses of Placebo from Day 1 to Day 14. Participants will also receive 2 mg Midazolam on Days -1, Day 1 and Day 14.
干预措施: Placebo (Drug)
Part B: Placebo MAD DDI group
Healthy participants will receive 14 daily repeat doses of Placebo from Day 1 to Day 14. Participants will also receive 2 mg Midazolam on Days -1, Day 1 and Day 14.
干预措施: Midazolam (Drug)
Part B: VH4770359 MAD Drug-Drug Interaction (DDI) group
Healthy participants will receive 14 daily repeat doses of VH4770359 from Day 1 to Day 14. Participants will also receive 2 mg Midazolam on Days -1, Day 1 and Day 14.
干预措施: Midazolam (Drug)
结局指标
主要结局
Number of participants with Grade 3 and Grade 4 adverse events (AEs)
时间窗: From Day 1 (first dose of study intervention) in each treatment period until the last on-site study visit (up to approximately 9 weeks)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The AEs are graded using the Division of Acquired Immunodeficiency Syndrome (DAIDS) criteria where grades are defined based on numeric criteria as follows Grade 3: severe symptoms; Grade 4: potentially life-threatening. A higher grade indicates greater severity.
次要结局
- Part A: Area under the curve from time zero extrapolated to infinity (AUC[0-inf]) of VH4770359 following single dose administration(At Day 1 (pre-dose, 0.5h 1h, 2h, 3h, 4h, 6h, 8h,12h), Day 2 (24h, 36h), Day 3, Day 4, Day 5, Day 6, Day 7 and during outpatient visits until the last on site study visit (up to approximately 9 weeks))
- Part B: AUC over a single dosing interval from time 0 to the next dose (AUC[0-tau]) of VH4770359 following multiple dose administration(At Day 1 (pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h) and at Day 14 (pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h))