A Phase 1 Open-label, Two-cohort, One-sequence Crossover Study to Investigator the Effect of P-glycoprotien Inhibitor (Itraconazole) and Inducer (Rifampin) on the Pharmacokinetics, Safety, and Tolerability of Sitravatinib in Health Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Pharmacokinetics - Vz/F (sitravatinib)
研究概览
简要总结
A Phase 1 Open-label, Two-cohort, One-sequence Crossover Study to Investigate the Effect of P glycoprotein Inhibitor (Itraconazole) and Inducer (Rifampin) on the Pharmacokinetics, Safety, and Tolerability of Sitravatinib in Healthy Subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 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
- •Body mass index between 18.0 and 32.0 kg/m2, inclusive.
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations at screening and/or check-in, as assessed by the investigator (or qualified designee).
- •Females of childbearing potential will not be pregnant or lactating and must have a negative result on an approved pregnancy test at screening and check-in. Females of childbearing potential must agree to use contraception.
- •Male subjects must agree to use contraception.
- •Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
排除标准
- •Significant history of clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator.
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, any components of the IMP, or other substance (not including seasonal allergies), unless approved by the investigator.
- •History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications. (Uncomplicated appendectomy and hernia repair are allowed. Cholecystectomy is not allowed.)
- •History of Gilbert's syndrome or suspicion of Gilbert's syndrome based on elevated total and indirect bilirubin (may be confirmed by repeat).
- •Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to study drug administration on Day 1 of Period 1.
研究组 & 干预措施
Group 1 Treatment A
A single-dose administration of sitravatinib malate 50 mg on Day 1. Day 12, a single dose of sitravatinib malate 50 mg will be will be followed by a 72-hour PK sample collection period. Subjects will be discharged from the CRU on Day 4 after collection of 72-hour postdose PK sample and completion of all required study procedures.
干预措施: Sitravatinib 50 mg (Drug)
Group 1 Treatment B
On Days 9 to 11, itraconazole 200 mg will be administered QD in the morning. On Day 12, a single dose of sitravatinib malate 50 mg will be coadministered with itraconazole. Itraconazole QD dosing will continue on Days 13 to 18 to maintain steady state during the PK sample collection period.
干预措施: Itraconazole (Drug)
Group 2 Treatment A
A single-dose administration of sitravatinib malate 100 mg on Day 1 will be followed by a 72-hour PK sample collection period. Subjects will be discharged from the CRU on Day 4 after collection of 72-hour postdose PK sample and completion of all required study procedures.
干预措施: Sitravatinib 100 mg (Drug)
Group 2 Treatment B
On Days 9 to 15, rifampin 600 mg will be administered QD in the morning. On Day 16, a single dose of sitravatinib malate 100 mg will be coadministered with rifampin followed by a 72 hour PK sample collection period. Rifampin QD dosing will continue on Days 17 to 22 to maintain steady state during the PK sample collection period.
干预措施: Rifampin (Drug)
结局指标
主要结局
Pharmacokinetics - Vz/F (sitravatinib)
时间窗: Up to 168 hours after dosing
Apparent volume of distribution when dosed orally
Pharmacokinetics - Cmax (sitravatinib)
时间窗: Up to Day 168 hours after dosing
Maximum observed plasma concentration
Pharmacokinetics - AUC∞ (sitravatinib)
时间窗: Up to 168 hours after dosing
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Pharmacokinetics - tmax (sitravatinib)
时间窗: Up to 168 hours after dosing
Terminal elimination half-life
Pharmacokinetics - uf (sitravatinib)
时间窗: Up to 168 hours after dosing
Unbound fraction
Pharmacokinetics - CL/F (sitravatinib)
时间窗: Up to 168 hours after dosing
Apparent total plasma clearance when dosed orally
Pharmacokinetics - AUClast (sitravatinib)
时间窗: Up to 168 hours after dosing
Area under the curve from time zero to the last measured time point
次要结局
- Adverse Events (AEs)(Up to 12 weeks from screening)