A Phase 1, Three-Part, Open-label Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug Interactions With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 134
- 试验地点
- 1
- 主要终点
- Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
研究概览
简要总结
This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin and simvastatin in healthy male and female subjects.
详细描述
This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin in healthy male and female subjects. Thirty-four (34) subjects will be enrolled in Part 1 (rosuvastatin) and based on review of the PK and safety/tolerability data, a decision will be made on whether to proceed with Part 2. Part 2 consists of 2 arms (sulfasalazine and pravastatin). Twenty-six (26) subjects will be enrolled into each arm. Part 3 consists of 2 arms (atorvastatin and simvastatin). Twenty-four (24) subjects will be enrolled into each arm after enrollment in Part 2 is completed. Subjects will be in the study for up to 72 days, including a 28-day screening period, 6-14 day in clinic period, and a 30-day follow up period post last dose. Blood samples for PK analysis will be collected at pre-defined time points throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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; History of latent or active tuberculosis (TB).
- •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
Rosuvastatin, Vadadustat
Part 1: Subjects will receive rosuvastatin 20 mg alone, vadadustat 600 mg alone, followed by rosuvastatin 20 mg in combination with vadadustat 600 mg in a fixed-sequence dosing design.
干预措施: Vadadustat (Drug)
Rosuvastatin, Vadadustat
Part 1: Subjects will receive rosuvastatin 20 mg alone, vadadustat 600 mg alone, followed by rosuvastatin 20 mg in combination with vadadustat 600 mg in a fixed-sequence dosing design.
干预措施: Rosuvastatin (Drug)
Sulfasalazine. Pravastatin, Vadadustat
Part 2, Arm 1: Subjects will receive sulfasalazine 500 mg alone followed by sulfasalazine 500 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
Part 2, Arm 2: Subjects will receive pravastatin 40 mg alone followed by pravastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
干预措施: Vadadustat (Drug)
Sulfasalazine. Pravastatin, Vadadustat
Part 2, Arm 1: Subjects will receive sulfasalazine 500 mg alone followed by sulfasalazine 500 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
Part 2, Arm 2: Subjects will receive pravastatin 40 mg alone followed by pravastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
干预措施: Pravastatin (Drug)
Sulfasalazine. Pravastatin, Vadadustat
Part 2, Arm 1: Subjects will receive sulfasalazine 500 mg alone followed by sulfasalazine 500 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
Part 2, Arm 2: Subjects will receive pravastatin 40 mg alone followed by pravastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
干预措施: Sulfasalazine (Drug)
Atorvastatin, Simvastatin, Vadadustat
Part 3, Arm 1: Subjects will receive atorvastatin 40 mg alone followed by atorvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
Part 3, Arm 2: 24 subjects will receive simvastatin 40 mg alone followed by simvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
干预措施: Vadadustat (Drug)
Atorvastatin, Simvastatin, Vadadustat
Part 3, Arm 1: Subjects will receive atorvastatin 40 mg alone followed by atorvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
Part 3, Arm 2: 24 subjects will receive simvastatin 40 mg alone followed by simvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
干预措施: Simvastatin (Drug)
Atorvastatin, Simvastatin, Vadadustat
Part 3, Arm 1: Subjects will receive atorvastatin 40 mg alone followed by atorvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
Part 3, Arm 2: 24 subjects will receive simvastatin 40 mg alone followed by simvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
干预措施: Atorvastatin (Drug)
结局指标
主要结局
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
时间窗: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
时间窗: Up to 10 weeks
Area under plasma concentration-time curve (AUCtau) of atorvastatin
时间窗: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of rosuvastatin. sulfasalazine, pravastatin, atorvastatin and simvastatin
时间窗: Up to 10 weeks
次要结局
- Time to maximum observed plasma concentration (Tmax) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin(Up to 10 weeks)
- Apparent total body clearance (CL/F) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin(Up to 10 weeks)
- Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine(Up to 10 weeks)
- Time to maximum observed plasma concentration (Tmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine(Up to 10 weeks)
- Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of simvastatin metabolite(Up to 10 weeks)
- Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of simvastatin metabolite(Up to 10 weeks)
- Terminal half-life (t½), of simvastatin metabolite(Up to 10 weeks)
- Terminal half-life (t½) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin(Up to 10 weeks)
- Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine(Up to 10 weeks)
- Percentage of extrapolated area under the curve from time t to infinity (%AUCextrap or Residual Area) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin(Up to 10 weeks)
- Maximum observed plasma concentration (Cmax) of simvastatin metabolite(Up to 10 weeks)
- Reporting of treatment emergent adverse events (TEAE) as reported by the study subjects(Up to 10 weeks)
- Elimination rate constant (Kel) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin(Up to 10 weeks)
- Terminal half-life (t½) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine(Up to 10 weeks)
- Area under the plasma concentration-time curve for a dosing interval (AUCtau) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin(Up to 10 weeks)
- Maximum observed plasma concentration (Cmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin(Up to 10 weeks)
- Elimination rate constant (Kel) of simvastatin metabolite(Up to 10 weeks)
- Time to maximum observed plasma concentration (Tmax) of simvastatin metabolite(Up to 10 weeks)
- Maximum observed plasma concentration (Cmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine(Up to 10 weeks)
- Elimination rate constant (Kel) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine(Up to 10 weeks)
- Time to maximum observed plasma concentration (Tmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin(Up to 10 weeks)