Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)
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.
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).
III. Determine the safety and tolerability of single and multiple daily doses of BR-DIM.
IV. Determine the pharmacokinetics of a single dose of BR-DIM and of the same dose after
chronic daily dosing.
V. Determine the pharmacokinetics of a single dose of BR-DIM and of the same dose after
chronic daily dosing.
I. To determine effects of BR-DIM on activities of glutathione-S-transferase (GST), a phase
2 enzyme, in lymphocytes.
OUTLINE: This is a randomized, double-blind study. Participants are stratified according to
gender. Participants are randomized to 1 of 2 intervention arms.
Arm I: Participants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks.
Arm II: Participants receive high-dose oral BR-DIM twice daily for 4 weeks.
In both arms, participants receive an oral probe-drug cocktail comprising caffeine (CYP1A2),
dextromethorphan (CYP2D6), buspirone (CYP3A4), losartan (CYP2C9), and fexofenadine
(P-glycoprotein) before randomization and after the first and last dose of BR-DIM.
Blood and urine are collected periodically for pharmacokinetic profiles of BR-DIM and probe
After completion of study intervention, participants are followed at 1 week.
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2
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.
Up to 1 week
University of Kansas
United States: Food and Drug Administration
|University of Kansas Medical Center||Kansas City, Kansas 66160-7353|