CYP3A4 Activity and Mineral Homeostasis

University of Washington

Status and phase: Completed; Early Phase 1

Conditions: Vitamin D and Calcium Homeostasis

Treatments: Other: Grapefruit Juice; Drug: Clarithromycin; Other: Placebo; Drug: Rifampin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02019875

R01GM063666 (U.S. NIH Grant/Contract)

STUDY00001894

Details and patient eligibility

About

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.

Full 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.

Enrollment: 92 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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92 participants in 6 patient groups, including a placebo group

Water

Placebo Comparator group

Description:

200 mL of water once a day for 14 days

Treatment:

Other: Placebo

Rifampin

Active Comparator group

Description:

Rifampin 600 mg once a day for 14 days

Treatment:

Drug: Rifampin

Grapefruit Juice

Active Comparator group

Description:

200 mL of grapefruit juice once a day for 14 days

Treatment:

Other: Grapefruit Juice

Grapefruit Juice Plus Rifampin

Active Comparator group

Description:

200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days

Treatment:

Drug: Rifampin

Other: Grapefruit Juice

Clarithromycin

Active Comparator group

Description:

Clarithromycin 250 mg twice a day for 14 days

Treatment:

Drug: Clarithromycin

Clarithromycin Plus Rifampin

Active Comparator group

Description:

Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days

Treatment:

Drug: Rifampin

Drug: Clarithromycin