A Clinical Drug-Drug Interaction Study to Evaluate the Effect of a Proton Pump Inhibitor, a Combined P-gp/CYP3A4 Inhibitor, and a CYP2C9 Inhibitor on the Pharmacokinetics of Vismodegib
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 92
- 主要终点
- Relative effect of fluconazole on the steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css)
研究概览
简要总结
This randomized, open-label, 4-arm, multiple-dose study will evaluate the effect of coadministration of a protein pump inhibitor, an inhibitor of P-glycoprotein and CYP3A4, or an inhibitor of CYP2C9 on the pharmacokinetics of vismodegib in healthy female subjects of non-childbearing potential. Subjects will be randomized to receive multiple oral doses of vismodegib, alone or in combination with multiple oral doses of either rabeprazole, itraconazole or fluconazole. Anticipated time on study treatment is up to 11 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Females of non-childbearing potential
- •Body mass index (BMI) 18 to 32 kg/m2, inclusive
- •In good health, determined by no clinically significant findings from medical history, physical examination. 12-lead ECG, and vital signs
- •Clinical laboratory evaluations, complete blood count and urinalysis within the normal range for the test laboratory, unless not deemed clinically significant by the investigator
- •Negative test for drugs of abuse at screening and check-in (including alcohol)
- •Negative for hepatitis B, hepatitis C and HIV infection
- •Non-childbearing potential is defined as: non-pregnant, non-lactating, and either postmenopausal for at least 1 year or surgically sterile (e.g. bilateral oophorectomy and/or hysterectomy)
排除标准
- •Significant history or clinical evidence of any metabolic (including type 1 or 2 diabetes). allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, endocrine, GI (including gastric or duodenal ulcers), Zollinger-Ellison syndrome, Barrett's esophagus, urological, neurological, or psychiatric disorder
- •History of inflammatory arthritis
- •History of symptomatic hypotension
- •History of seizure disorders
- •History of bipolar or major depressive disorder
- •History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
- •History of alcoholism or drug addiction within 1 year prior to check-in
- •Use of any tobacco- or nicotine-containing products within 6 months prior to check-in
- •Participation in any other investigational study drug or biological agent trial in which receipt of investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, prior to check-in
- •Use of PPIs, H2-receptor antagonists, or antacids within 1 month prior to check-in
- •History of chronic PPI use (> 30 days of continuous daily dosing) within 6 months of check-in
研究组 & 干预措施
A: Vismodegib
干预措施: vismodegib (Drug)
B: Rabeprazole + Vismodegib
干预措施: rabeprazole (Drug)
B: Rabeprazole + Vismodegib
干预措施: vismodegib (Drug)
C: Itraconazole + Vismodegib
干预措施: itraconazole (Drug)
C: Itraconazole + Vismodegib
干预措施: vismodegib (Drug)
D: Fluconazole + Vismodegib
干预措施: fluconazole (Drug)
D: Fluconazole + Vismodegib
干预措施: vismodegib (Drug)
结局指标
主要结局
Relative effect of fluconazole on the steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css)
时间窗: up to 12 days
Relative effect of rabeprazole on steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css)
时间窗: up to 12 days
Relative effect of itraconazole on steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css)
时间窗: up to 12 days
次要结局
未报告次要终点