Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2
研究概览
简要总结
This randomized phase I trial is studying the side effects and best dose of diindolylmethane in healthy volunteers. Chemoprevention is the use of certain drugs or substances to keep cancer from forming, growing, or coming back. The use of diindolylmethane may keep cancer from forming. Collecting and storing samples of blood and urine from healthy volunteers to study in the laboratory may help doctors learn more about the way a person's body handles the drug.
详细描述
PRIMARY OBJECTIVES:
I. Determine the effect of multiple daily dosing with nutritional-grade, absorption-enhanced diindolylmethane (BR-DIM) on the disposition of probe drugs metabolized by cytochrome P4501A2 (CYP1A2) and CYP3A4 in healthy volunteers.
SECONDARY OBJECTIVES:
I. Determine the effect of multiple daily doses of BR-DIM on estrogen metabolites in urine and on activities of CYP2C9, CYP2D6, and P-glycoprotein/OATP.
II. Determine the effect of a single dose of BR-DIM on the disposition of probe drugs that are metabolized or transported by CYP1A2, CYP2C9, CYP2D6, CYP3A4, and P-glycoprotein (P-go).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm I (low-dose oral diindolylmethane)
Participants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks.
干预措施: oral microencapsulated diindolylmethane (Drug)
Arm II (high-dose oral diinolylmethane)
Participants receive high-dose oral BR-DIM twice daily for 4 weeks.
干预措施: oral microencapsulated diindolylmethane (Drug)
结局指标
主要结局
Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2
时间窗: Up to 1 week
Descriptive statistics will be calculated on all variables of interest: frequencies and percentages will be used to summarize categorical variables and medians, and ranges will summarize quantitative variables. Paired t-tests will be used to compare enzyme levels post-pre at each dose. Analysis of covariance will be used to determine if there is a dose effect on enzyme levels, using the baseline values as a covariate. If there is no dose effect, the seven subjects at each dose will be pooled which will provide an increase power to detect meaningful changes in enzyme levels.
Grade 2 or higher toxicities, graded using NCI CTC version 2.0
时间窗: Up to 1 week
A one-sided binomial test will be used. Descriptive statistics will be calculated on all variables of interest: frequencies and percentages will be used to summarize categorical variables and medians, and ranges will summarize quantitative variables.
Steady-state pharmacokinetic parameters such as half-life, Cmax, Tmax, and AUC
时间窗: Up to 1 week
Pharmacokinetic parameters between pre- and post-menopausal women will be compared using the Wilcoxon rank-sum test.
次要结局
- Drug metabolizing enzyme values (CYP2C9, CYP2D6, P-glycoprotein/OATP, and glutathione-S-transferase)(Up to 1 week)
- 2/16 alpha OHE ratio in urine(Up to 1 month)