A Phase 1 Open-label, Three Arm Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug-Interactions With Digoxin, Adefovir and Furosemide
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide
研究概览
简要总结
This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy male and female subjects.
详细描述
This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy male and female subjects. Unique subjects will be enrolled into each arm of the study and enrollment will be sequential. The first 20 subjects confirmed to be eligible will be assigned to Arm 1 (digoxin), the next 16 subjects will be assigned to Arm 2 (adefovir) and the next 22 subjects will be assigned to Arm 3 (furosemide). Blood samples for PK analysis will be collected at pre-defined timepoints for each arm throughout the study. Subjects will be on study for up to 80 days, including a 28-day screening period, 7-21 day in clinic period, and a 30-day follow up period post last dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
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
- •Healthy Male or female between 18 and 55 years of age, inclusive, at time of informed consent.
- •Body mass index between 18.0 and 30.0 kg/m2, with a minimum body weight of 45 kg for females and 50 kg for males, inclusive.
排除标准
- •Current or past clinically significant history of cardiovascular, cerebrovascular, pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease. History of cancer (except treated non-melanoma skin cancer) or history of chemotherapy use within 5 years prior to Screening.
- •Positive test results for human immunodeficiency virus (HIV) antibody; Positive test results of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus antibody (HCVab) within 3 months prior to screening; or positive test results for human immunodeficiency virus antibody (HIVab) at Screening
- •Taking any prescription medication or over the counter multi-vitamin supplement, or any non-prescription products (including herbal-containing preparations but excluding acetaminophen) within 14 days prior to Day -1.
研究组 & 干预措施
Vadadustat, digoxin
Arm 1: Subjects will receive a single oral dose of digoxin 0.5 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of digoxin 0.5 mg.
干预措施: Vadadustat (Drug)
Vadadustat, digoxin
Arm 1: Subjects will receive a single oral dose of digoxin 0.5 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of digoxin 0.5 mg.
干预措施: Digoxin (Drug)
Vadadustat, adefovir
Arm 2: Subjects will receive a single dose of oral adefovir 10 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of adefovir.
干预措施: Vadadustat (Drug)
Vadadustat, adefovir
Arm 2: Subjects will receive a single dose of oral adefovir 10 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of adefovir.
干预措施: Adefovir (Drug)
Vadadustat, Furosemide
Arm 3: Subjects will receive a single dose of oral furosemide 40 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone, and in combination with a single dose of furosemide 40 mg.
干预措施: Vadadustat (Drug)
Vadadustat, Furosemide
Arm 3: Subjects will receive a single dose of oral furosemide 40 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone, and in combination with a single dose of furosemide 40 mg.
干预措施: Furosemide (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide
时间窗: Up to 12 Weeks
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide
时间窗: Up to 12 Weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide
时间窗: Up to 12 Weeks
次要结局
- Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide(Up to 12 Weeks)
- Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide(Up to 12 Weeks)
- Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects(Up to 12 Weeks)
- Terminal half-life (t½) for digoxin, adefovir and furosemide(Up to 12 Weeks)
- Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide(Up to 12 Weeks)
- Elimination rate constant (Kel) for digoxin, adefovir and furosemide(Up to 12 Weeks)