Effect of Modulating CYP3A4 Activity on Mineral Homeostasis
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Calcium/Creatinine (mg/g)
研究概览
简要总结
The purpose of this study is to determine whether changes in the activity of the enzyme CYP3A4 can change the Vitamin D and bone mineral homeostasis.
详细描述
Healthy volunteers will receive one of six interventions for 14 days (determined by randomization):a). 200 mL of water once a day; b) rifampin 600 mg once a day; c) 200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days; d) clarithromycin 250 mg twice a day; f) clarithromycin 250 mg twice a day plus rifampin 600 mg once a day.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects with no history of significant medical conditions including cardiac, pulmonary, gastrointestinal, or renal disease, HIV, diabetes mellitus or Hepatitis B or C
- •Subjects will be males or females 18-60 years of age
- •Subjects must read and understand English
- •Subjects must be able to provide informed consent
- •Subjects must be willing to avoid prescription medications, OTC drugs, dietary supplements and foods that are known to modulate CYP3A4 expression or activity
- •Subjects must be willing to maintain a consistent consumption of calcium and Vitamin D during the study and maintain a daily logbook of their dietary consumption
- •Women not currently pregnant or lactating. In addition, women participants of childbearing age must be willing to utilize a barrier method of birth control (sterilization will be acceptable)
- •Subjects will have no known allergies to the study drugs to be used
- •Subject's corrected QTc interval obtained by electrocardiogram will be ≤ 430 ms in men or ≤ 450 ms in women
排除标准
- •Subjects with any significant chronic medical condition, including cardiac, pulmonary, gastrointestinal, or renal disease, HIV, diabetes mellitus or Hepatitis B or C
- •Subjects less than 18 or greater than 60 years of age
- •Subjects unable to read and understand English
- •Subjects unable to provide informed consent
- •Subjects unable to avoid prescription medications, OTC drugs, dietary supplements and foods that are known to modulate CYP3A4 expression or activity
- •Subjects not willing to maintain a consistent consumption of calcium and Vitamin D during the study and maintain a daily logbook of their dietary consumption
- •Women who are pregnant or lactating and women participants of childbearing age not willing to utilize a barrier method of birth control (sterilization will be acceptable)
- •Subjects with allergies to rifampin, clarithromycin or grapefruit juice
- •Potential participants will be excluded if they are concurrently participating in another research study
- •Subjects with corrected QTc interval > 430 ms in men or > 450 ms in women on electrocardiogram
研究组 & 干预措施
Water
200 mL of water once a day for 14 days
干预措施: Placebo (Other)
Rifampin
Rifampin 600 mg once a day for 14 days
干预措施: Rifampin (Drug)
Grapefruit Juice
200 mL of grapefruit juice once a day for 14 days
干预措施: Grapefruit Juice (Other)
Grapefruit Juice Plus Rifampin
200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days
干预措施: Rifampin (Drug)
Grapefruit Juice Plus Rifampin
200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days
干预措施: Grapefruit Juice (Other)
Clarithromycin
Clarithromycin 250 mg twice a day for 14 days
干预措施: Clarithromycin (Drug)
Clarithromycin Plus Rifampin
Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days
干预措施: Rifampin (Drug)
Clarithromycin Plus Rifampin
Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days
干预措施: Clarithromycin (Drug)
结局指标
主要结局
Calcium/Creatinine (mg/g)
时间窗: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
Urine Calcium/Creatinine (mg/g)
Calcium, Ionized
时间窗: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
Serum
1, 25(OH) D3 Vitamin D
时间窗: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
Serum 1, 25(OH) D3 Vitamin D
Osteocalcin
时间窗: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
Serum Osteocalcin
25(OH) D3 Vitamin D
时间窗: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
Serum 25(OH) D3 Vitamin D
Parathyroid Hormone
时间窗: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
Blood Parathyroid Hormone
Phosphate/Creatinine (mg/g)
时间窗: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
Urine Phosphate/Creatinine(mg/g)
次要结局
未报告次要终点
研究者
Kenneth Thummel
Professor, Department of Pharmaceutics
University of Washington