CYP3A4 Activity and Mineral Homeostasis

Early Phase 1

Completed

Conditions: Vitamin D and Calcium Homeostasis

Interventions: Other: Grapefruit Juice
Other: Placebo
Drug: Rifampin
Drug: Clarithromycin

Registration Number: NCT02019875

Lead Sponsor: University of Washington

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 92

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Grapefruit Juice	Grapefruit Juice	200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice Plus Rifampin	Grapefruit Juice	200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days
Water	Placebo	200 mL of water once a day for 14 days
Rifampin	Rifampin	Rifampin 600 mg once a day for 14 days
Grapefruit Juice Plus Rifampin	Rifampin	200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days
Clarithromycin	Clarithromycin	Clarithromycin 250 mg twice a day for 14 days
Clarithromycin Plus Rifampin	Rifampin	Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days
Clarithromycin Plus Rifampin	Clarithromycin	Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days

Primary Outcome Measures

Name	Time	Method
Calcium/Creatinine (mg/g)	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	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	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	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	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	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)	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)