Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD), defined as the highest dose at which no grade 2 or higher toxicities are seen
研究概览
简要总结
This phase I clinical trial studies the side effects and best dose of diindolylmethane in preventing cancer in healthy volunteers. Diindolylmethane is formed in the stomachs of people who eat a chemical that is normally found in vegetables, including cabbage, broccoli, Brussels sprouts, cauliflower, and watercress. Diindolylmethane may prevent the development of cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine single oral doses of 3,3' di-indolylmethane (DIM) (diindolylmethane) that are safe and well- tolerated.
II. To determine the pharmacokinetics of these single oral doses of DIM.
OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.
ARM I: Participants receive a single dose of diindolylmethane orally (PO) on day 1.
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
- •Non-smokers and non-users of abuse drugs as confirmed by urine cotinine (Accutest NicoMeter Urine Professional strip or equivalent test) and drug screen at visit 1
- •Free of acute, unstable, chronic or recurring medical conditions based on history, physical examination, laboratory tests; the laboratory tests to be performed will be: blood serum chemistry screen to include comprehensive metabolic panel (glucose, creatinine, urea nitrogen [blood urea nitrogen (BUN)], sodium, potassium, chloride, calcium, total bilirubin, protein, albumin, globulin, cholesterol and the enzymes alkaline phosphatase, aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) and lipid panel (total, low density lipoprotein [LDL] and high density lipoprotein [HDL] cholesterol and triglycerides); complete blood count including differential and platelet count; prothrombin time; and routine urinalysis; values for laboratory tests must be within the ranges below grade 2 of Common Toxicity Criteria (CTC) and/or as specified below:
- •Hemoglobin > 10 g/dL
- •Absolute granulocyte count > 1500/ìL
- •Creatinine < 2.0 mg/dl
- •Albumin > 3.0 g/dl
- •Bilirubin < 1.8 mg/dl
- •AST < 110 U/l
- •ALT < 110 U/l
- •Alkaline phosphatase < 300 U/l
- •Subjects must weigh +/- 20% of ideal body weight by the Metropolitan Life tables
- •Men or women who are strict vegetarians or who eat more than 3 medium servings (1/2 cup each) of cruciferous vegetables per week will be excluded; those who stop ingesting cruciferous vegetables >= 14 days and alcohol >= 7 days before starting DIM and agree to refrain from taking them for the duration of the study will not be excluded; cruciferous vegetables include broccoli, cabbage (including coleslaw), cauliflower, bok-choy, Brussels sprouts, collards, kale, kohlrabi, mustard greens, rutabaga, turnip, and watercress; participants will be asked to complete a brief diet questionnaire listing these vegetables to assess these criteria; caffeine- and grapefruit-containing foods and beverages are to be avoided for at least 48 hours before visit 2 (DIM dosing)
排除标准
- •Subjects with serious drug allergies or other serious intolerance or allergies will be excluded; those with mild seasonal allergies will be accepted
- •Subjects with chronic headaches, dysphoria, fatigue, dizziness, blurred vision, insomnia, rhinorrhea, nausea, vomiting, abdominal pain, diarrhea, constipation, or similar conditions
- •Subjects with a serious acute or chronic illness (diabetes, arthritis, asthma, etc.) or requiring chronic drug therapy, who continuously take supplements or have taken an investigational drug within the past three months
- •Subjects who have evidence of an active malignancy or have received chemotherapy, and/or antiestrogen therapy
- •Subjects who have a life expectancy of < 12 months
- •Subjects who have regularly taken over the past 21 days any concomitant medications, herbal products, dietary supplements or vitamins; women taking oral contraceptives will be accepted; women who are pregnant (positive urine human chorionic gonadotropin [hCG] at visit 2) or lactating will be excluded
研究组 & 干预措施
Arm I (diindolylmethane)
Participants receive a single dose of diindolylmethane PO on day 1.
干预措施: diindolylmethane (Drug)
Arm I (diindolylmethane)
Participants receive a single dose of diindolylmethane PO on day 1.
干预措施: pharmacological study (Other)
Arm I (diindolylmethane)
Participants receive a single dose of diindolylmethane PO on day 1.
干预措施: laboratory biomarker analysis (Other)
Arm I (diindolylmethane)
Participants receive a single dose of diindolylmethane PO on day 1.
干预措施: quality-of-life assessment (Other)
Arm II (placebo)
Participants receive a single dose of placebo orally (PO) on day 1.
干预措施: placebo (Other)
Arm II (placebo)
Participants receive a single dose of placebo orally (PO) on day 1.
干预措施: pharmacological study (Other)
Arm II (placebo)
Participants receive a single dose of placebo orally (PO) on day 1.
干预措施: laboratory biomarker analysis (Other)
Arm II (placebo)
Participants receive a single dose of placebo orally (PO) on day 1.
干预措施: quality-of-life assessment (Other)
结局指标
主要结局
Maximum tolerated dose (MTD), defined as the highest dose at which no grade 2 or higher toxicities are seen
时间窗: Up to day 6
Frequencies and percents will be used to summarize the toxicities seen at each dose level and overall. 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.
次要结局
- Pharmacokinetics of diindolylmethane(Baseline and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after administration)