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CYP3A4 Induction and Mineral Homeostasis

Sponsor
University of Washington (Other)
Overall Status
Completed
CT.gov ID
NCT02019875
Collaborator
(none)
91
Enrollment
1
Location
6
Arms
78
Duration (Months)
1.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
91 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Hormonal Regulation of CYP3A
Study Start Date :
Jun 1, 2014
Actual Primary Completion Date :
Dec 1, 2020
Actual Study Completion Date :
Dec 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Water

200 mL of water once a day for 14 days

Other: Placebo
Active Comparator: Rifampin

Rifampin 600 mg once a day for 14 days

Drug: Rifampin
P450 inducer
Other Names:
  • Rifadin

    		•
    Active Comparator: Grapefruit Juice

    200 mL of grapefruit juice once a day for 14 days

    Other: Grapefruit Juice
    CYP3A4 inhibitor in intestine
    Active Comparator: 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

    Drug: Rifampin
    P450 inducer
    Other Names:
  • Rifadin

    • Other: Grapefruit Juice
    CYP3A4 inhibitor in intestine
    Active Comparator: Clarithromycin

    Clarithromycin 250 mg twice a day for 14 days

    Drug: Clarithromycin
    CYP3A4 and Pgp inhibitor in both intestine and liiver
    Other Names:
  • Biaxin

    		•
    Active Comparator: Clarithromycin Plus Rifampin

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

    Drug: Rifampin
    P450 inducer
    Other Names:
  • Rifadin

    • Drug: Clarithromycin
    CYP3A4 and Pgp inhibitor in both intestine and liiver
    Other Names:
  • Biaxin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 1, 25(OH) D3 Vitamin D [Samples will be collected on day 1, day 4, day 7, day 8 (first day of intervention), day 9, day 11, day 15, day 18, day 22 (last day of intervention), day 24, day 26, day 29, day 32 and day 36.]

      Serum

    2. 25(OH) D3 Vitamin D [Samples will be collected on day 1, day 4, day 7, day 8 (first day of intervention), day 9, day 11, day 15, day 18, day 22 (last day of intervention), day 24, day 26, day 29, day 32 and day 36.]

      Serum

    3. Parathyroid Hormone [Samples will be collected on day 1, day 4, day 7, day 8 (first day of intervention), day 9, day 11, day 15, day 18, day 22 (last day of intervention), day 24, day 26, day 29, day 32 and day 36.]

      Blood

    4. Osteocalcin [Samples will be collected on day 1, day 4, day 7, day 8 (first day of intervention), day 9, day 11, day 15, day 18, day 22 (last day of intervention), day 24, day 26, day 29, day 32 and day 36.]

      Serum

    5. Calcium, total [Samples will be collected on day 1, day 4, day 7, day 8 (first day of intervention), day 9, day 11, day 15, day 18, day 22 (last day of intervention), day 24, day 26, day 29, day 32 and day 36.]

      Serum

    6. Calcium, ionized [Samples will be collected on day 1, day 4, day 7, day 8 (first day of intervention), day 9, day 11, day 15, day 18, day 22 (last day of intervention), day 24, day 26, day 29, day 32 and day 36.]

      Serum

    7. Calcium [Samples will be collected on day 1, day 4, day 7, day 8 (first day of intervention), day 9, day 11, day 15, day 18, day 22 (last day of intervention), day 24, day 26, day 29, day 32 and day 36.]

      Urine

    8. Phosphate [Samples will be collected on day 1, day 4, day 7, day 8 (first day of intervention), day 9, day 11, day 15, day 18, day 22 (last day of intervention), day 24, day 26, day 29, day 32 and day 36.]

      Urine

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Washington Seattle Washington United States 98195

    Sponsors and Collaborators

    • University of Washington

    Investigators

    • Principal Investigator: Kenneth Thummel, Ph.D., University of Washington

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kenneth Thummel, Professor, Department of Pharmaceutics, University of Washington
    ClinicalTrials.gov Identifier:
    NCT02019875
    Other Study ID Numbers:
    • STUDY00001894
    First Posted:
    Dec 24, 2013
    Last Update Posted:
    Dec 22, 2020
    Last Verified:
    Dec 1, 2020
    Keywords provided by Kenneth Thummel, Professor, Department of Pharmaceutics, University of Washington
    Vitamin D
    CYP3A4
    Calcium
    Additional relevant MeSH terms:
    Clarithromycin
    Rifampin

    Study Results

    No Results Posted as of Dec 22, 2020