A Phase 1, Open-Label Study to Evaluate the Relative Bioavailability and the Effect of Food on VH4524184 Tablet Formulations, and to Evaluate the Potential for VH4524184 Drug-Drug-Interactions in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 2
- 主要终点
- Part 1: Maximum plasma concentration (Cmax) for VH4524184
研究概览
简要总结
The aim of the study is to gather information on how the drug behaves in healthy adults, how it is absorbed, and how it interacts when taken with other medicines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •1. Participants must be 18 to 60 years of age inclusive at the time of signing the Informed consent form (ICF).
- •2. Male or female
- •Male Participants: No restrictions for male participants
- •A female participant (female sex assigned at birth) is eligible to participate if she is not pregnant, or breastfeeding and the following condition applies: She is a woman of nonchildbearing potential (WONCBP).
- •3. Participants who are overtly healthy as determined by medical evaluation
- •AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5 x Upper Limit of Normal (ULN)
- •Capable of giving signed informed consent.
排除标准
- •History or presence of clinical conditions affecting drug absorption, metabolism, or elimination.,
- •Pre-existing clinically relevant, gastro-intestinal pathology
- •Abnormal glucose metabolism requiring insulin or medications.
- •Clinically significant Abnormal blood pressure.
- •History of Lymphoma, leukemia, or any malignancy within the past 5 years (3 years for resected basal or squamous epithelial carcinomas of skin).
- •Breast cancer within the past 10 years.
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities.
- •History of syncope, clinically significant palpitations, cardiac arrhythmias or cardiac disease or a family long QT syndrome.
- •History of seizure(s) and / or other clinically significant neurological conditions.
- •Pre-existing psychiatric condition, including depression, anxiety, and/or insomnia/sleep disturbances and / or suicidal ideation.
- •History of drug hypersensitivity.
- •13. Use of medications/supplements affecting cytochrome P450 enzymes within 7 to 14 days prior to dosing.
- •14. Contraindications based on selected drug prescribing information.
- •Exposure to more than 4 new investigational products within 12 months
- •Current enrollment or past participation in another investigational study in which an investigational intervention was administered within the last 30 days.
- •17. Estimated glomelular filtration rate (eGFR) < 90 mL/min or serum creatinine >1.1×ULN [Inker, 2021].
- •18. Hemoglobin <12.5 g/dL for men and <11 g/dL for women.
- •Presence of Hepatitis B surface antigen (HBsAg) [and Hepatitis B core antibody (HBcAb)] at screening
- •Positive Hepatitis C antibody test result at screening
- •Positive SARS-CoV-2 test, having signs and symptoms which in the opinion of the investigator are suggestive of COVID-
- •22.Positive pre- study drug/alcohol screen.
- •Poor metabolizers of CYP2C9 and / or CYP2C19 as assessed by genotype testing. HLA-B*1502 positive as applicable to specified cohort.
- •Other exclusion criteria
- •Regular alcohol consumption exceeding specified limits.
- •Regular use of known drugs of abuse.
- •Nicotine use within 6 months.
- •Sensitivity or allergy to the study drug.
- •ALT >1.5×ULN.
- •Total bilirubin >1.5×ULN.
- •Significant arrhythmias or ECG findings that may compromise participant safety according to the investigator or VH Medical Monitor's assessment.
- •31. For eligibility determination, triplicate ECGs are required. The criteria are:
- •Heart Rate: Excludes males with <45 or >100 bpm, females with <50 or >100 bpm.
- •PR Interval: Excludes any PR intervals <120 or >220 msec.
- •QRS Duration: Excludes durations <70 or >120 msec.
- •QTcF Interval: Excludes intervals >450 msec.
研究组 & 干预措施
Part 2_Cohort 2A
Participants will receive VH4524184 and Rifabutin.
干预措施: Rifabutin (Drug)
Part 2_Cohort 1
Participants will receive VH4524184 tablet and Itraconazole.
干预措施: Itraconazole (Drug)
Part 2_Cohort 2A
Participants will receive VH4524184 and Rifabutin.
干预措施: VH4524184 (Drug)
Part 1A_VH4524184 (Sequence 1)
Participants will receive VH4524184 tablet(s) of Dose level 1 followed by Dose level 2 in fasted condition.
干预措施: VH4524184 (Drug)
Part 1A_VH4524184 (Sequence 2)
Participants will receive VH4524184 tablet(s) of Dose level 2 followed by Dose level 1 in fasted condition.
干预措施: VH4524184 (Drug)
Part 1A_VH4524184 (Sequence 3)
Participants will receive VH4524184 tablet(s) of Dose level 3 followed by Dose level 2 in fasted condition.
干预措施: VH4524184 (Drug)
Part 1A_VH4524184 (Sequence 4)
Participants will receive VH4524184 tablet(s) of Dose level 2 followed by Dose level 3 in fasted condition.
干预措施: VH4524184 (Drug)
Part 1B_VH4524184 (Sequence 5)
Participants will receive VH4524184 tablet of Dose level 2 in fasted condition and then followed by intake of a high fat meal.
干预措施: VH4524184 (Drug)
Part 1B_VH4524184 Sequence 6)
Participants will receive VH4524184 tablet of Dose level 2 following a high fat meal and then in fasted condition.
干预措施: VH4524184 (Drug)
Part 1B_VH4524184 (Sequence 7)
Participants will receive VH4524184 tablet of Dose level 3 in fasted condition and then followed by intake of a high fat meal.
干预措施: VH4524184 (Drug)
Part 1B_VH4524184 (Sequence 8)
Participants will receive VH4524184 tablet of Dose level 3 following a high fat meal and then in a fasted condition.
干预措施: VH4524184 (Drug)
Part 2_Cohort 1
Participants will receive VH4524184 tablet and Itraconazole.
干预措施: VH4524184 (Drug)
Part 2_Cohort 2B
Participants will receive VH4524184 tablet and Phenytoin.
干预措施: VH4524184 (Drug)
Part 2_Cohort 2B
Participants will receive VH4524184 tablet and Phenytoin.
干预措施: Phenytoin (Drug)
Part 2_ Cohort 3
Participants will receive Metformin, Digoxin and VH4524184 tablets.
干预措施: VH4524184 (Drug)
Part 2_ Cohort 3
Participants will receive Metformin, Digoxin and VH4524184 tablets.
干预措施: Metformin (Drug)
Part 2_ Cohort 3
Participants will receive Metformin, Digoxin and VH4524184 tablets.
干预措施: Digoxin (Drug)
结局指标
主要结局
Part 1: Maximum plasma concentration (Cmax) for VH4524184
时间窗: Up to Day 18
Part 1: Area under the concentration-time curve from 0 to tau (AUC0-t) for VH4524184
时间窗: Up to day 18
Part 1: Area under the concentration-time curve from 0 to infinity (AUC0-inf) for VH4524184
时间窗: Up to day 18
Part 2: Cmax for VH4524184
时间窗: At Day 1, Day 14, Day 19 and Day 22
Part 2: AUC0-t of VH4524184
时间窗: At Day 1, Day 14, Day 19 and Day 22
Part 2: AUC0-inf of VH4524184
时间窗: At Day 1, Day 14, Day 19 and Day 22
Part 2: Cmax for metformin
时间窗: At Day 1 and Day 15
Part 2: AUC0-t for metformin
时间窗: At Day 1 and Day 15
Part 2: Cmax for Digoxin
时间窗: At Day 1 and Day 15
Part 2: AUC0-t for Digoxin
时间窗: At Day 1 and Day 15
次要结局
- Part 2: AUC0-t for VH5424184 Following Comedication with Transporter Substrates metformin and digoxin(At Day 1 and Day 15)
- Number of participants with adverse events (AEs) and severity of AEs(From Day 1 up to Day 42)
- Number of participants with AEs leading to discontinuation of study intervention(Throughout the study treatment period (from Day 1 up to Day 33))
- Number of participants with Change in laboratory parameters(From Day 1 up to Day 42)
- Number of participants with maximum toxicity grade increase from baseline in laboratory parameters(From Day 1 up to Day 42)
- Part 1: Time to maximum concentration (Tmax) of VH4524184(At Day 1)
- Part 1: Apparent Terminal Half Life (T1/2) of VH4524184(At Day 1)
- Part 1: Apparent oral clearance (CL/F) of VH4524184(At Day 1)
- Part 2: Tmax of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin)(At Day 1, Day 14, Day 19 and Day 22)
- Part 2: T1/2 of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin)(At Day 1, Day 14, Day 19 and Day 22)
- Part 2: CL/F of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin)(At Day 1, Day 14, Day 19 and Day 22)
- Part 2: Cmax for VH5424184 Following Comedication with Transporter Substrates with metformin and digoxin(At Day 1 and Day 15)
- Part 2: Cmax for Itraconazole Following Comedication with VH4524184(At Day 1 and Day 14)
- Part 2: AUC0-t for Itraconazole Following Comedication with VH4524184(At Day 1 and Day 14)
- Part 2: Cmax for Rifabutin Following Comedication with VH4524184(At Day 1 and Day 11)
- Part 2: AUC0-t for Rifabutin Following Comedication with VH4524184(At Day 1 and Day 19)
- Part 2: Cmax for Phenytoin Following Comedication with VH4524184(Day 1 and Day 22)
- Part 2: AUC0-t for Phenytoin Following Comedication with VH4524184(Day 1 and Day 22)