Evaluation of Food Effect on Pharmacokinetics of GDC-0449, an Inhibitor of Hedgehog Signaling
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Tmax'Following Single Dose of Drug
研究概览
简要总结
This randomized clinical trial studies the effect of food on the pharmacokinetics of vismodegib. Studying the effects of meals on the absorption of vismodegib may help doctors prescribe correct doses and label the drug accurately.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the effect of prandial states on the pharmacokinetic parameters of GDC-0449 (vismodegib).
II. To evaluate the effect of fat content of meals on the pharmacokinetic parameters of GDC-0449.
SECONDARY OBJECTIVES:
I. To evaluate the effect of prandial states and fat content of meals on the safety profile of GDC-0449.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed advanced malignancies (except for leukemias) refractory to standard of care therapy, or for whom no standard of care therapy is available
- •Measurable or non-measurable disease
- •An anticipated life expectancy > 3 months
- •Karnofsky performance status of > 70%
- •Leukocytes >= 3,000/mcL
- •Absolute neutrophil count >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Total bilirubin within normal institutional limits
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- •Creatinine =< 1.5 X institutional upper limit of normal
- •Women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 12 months post-treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 48 hours prior to the first dose of GDC-0449 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449
- •Female subjects of childbearing potential are defined as follows:
- •Patients with regular menses
- •Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding
- •Women who have had tubal ligation
- •Female subjects may be considered to NOT be of childbearing potential for the following reasons:
- •The patient has undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy or bilateral oophorectomy
- •The patient is medically confirmed to menopausal (no menstrual period) for 24 consecutive months
- •Pre-pubertal females; the parent or guardian of young female patients who have not yet started menstruation should verify that menstruation has not begun; if a young female patient reaches menarche during the study, then she is to be considered as a woman of childbearing potential from that time forward
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients may not be receiving any other investigational agents
- •Patients with known brain metastases should be excluded from this clinical trial
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in study
- •Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules
- •Patients with clinically important history of liver disease, including viral or other hepatitis or cirrhosis are ineligible
- •Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with GDC-0449
- •Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- •Patients with medical conditions that require the following medications will be excluded
- •Strong inhibitors of cytochrome P450 3A4 (CYP3A4) (clarithromycin, itraconazole, ketoconazole, nefazodone, erythromycin, grapefruit juice, verapamil, and diltiazem)
- •Strong inhibitors of cytochrome P450 2C9 (CYP2C9) (fluconazole and amiodarone)
- •Inducers of CYP3A4 (carbamazepine, dexamethasone, modafinil, oxcarbazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, troglitazone)
- •Inducers of CYP2C9 (rifampin, and secobarbital)
- •Patients who have a medical condition or dietary restrictions that prevent him or her from fasting for at least 10 hours (overnight) or eating a high calorie meal
- •Any ambiguity in the inclusion/exclusion criteria should be clarified and resolved by communication with the study investigators
研究组 & 干预措施
Arm I (vismodegib on empty stomach)
Patients receive a single dose of vismodegib PO on an empty stomach. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28.
干预措施: Pharmacological Study (Other)
Arm I (vismodegib on empty stomach)
Patients receive a single dose of vismodegib PO on an empty stomach. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28.
干预措施: Vismodegib (Drug)
Arm II (vismodegib after high fat meal)
Patients receive a single dose of vismodegib PO after eating a high fat meal. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28.
干预措施: Pharmacological Study (Other)
Arm II (vismodegib after high fat meal)
Patients receive a single dose of vismodegib PO after eating a high fat meal. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28.
干预措施: Vismodegib (Drug)
Arm III (vismodegib after low fat meal)
Patients receive a single dose of vismodegib PO after eating a low fat meal. Beginning 7 days later, patients receive vismodegib PO after eating a meal daily on days 1-28.
干预措施: Pharmacological Study (Other)
Arm III (vismodegib after low fat meal)
Patients receive a single dose of vismodegib PO after eating a low fat meal. Beginning 7 days later, patients receive vismodegib PO after eating a meal daily on days 1-28.
干预措施: Vismodegib (Drug)
结局指标
主要结局
Tmax'Following Single Dose of Drug
时间窗: 168 hours
Time of maximum drug concentration
Cmax Following Steady State Exposure for 14 Days
时间窗: 24 hours
Maximum drug concentration over 24 hours.
Tmax Following Steady State Exposure for 14 Days
时间窗: 24 hours
Time of maximum drug concentration.
Cmax Following Single Dose of Drug
时间窗: 168 hours
Highest observed concentration over the 168 hour period. Blood samples were collected at j0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 24, 48, 120, and 168 hours.
AUC Following Steady State Exposure for 14 Days
时间窗: 24 hours
Area under the curve from 0 to 24 hours.
AUC Following Single Dose of Drug
时间窗: 168 hours
Area under the curve from 0-168 hours.
Tlag Following Single Dose of Drug
时间窗: 168 hours
Time between drug administration and when it is first observed in the systemic circulation.
Ctrough Following Steady State Exposure for 14 Days
时间窗: 24 hours
Minimum blood concentration over 24-hour observation period. Blood sample collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 24 hours.
次要结局
- Objective Responses in Patients With Solid Tumors(Up to 30 days)