CYP3A4 Activity and Mineral Homeostasis

NCT02019875 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: STUDY00001894R01GM063666
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Vitamin D and Calcium Homeostasis

Keywords

Vitamin D; CYP3A4; Calcium

Outcome Measures

Primary Outcomes (7)

• 1, 25(OH) D3 Vitamin D

  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).

• 25(OH) D3 Vitamin D

  Serum 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).

• Parathyroid Hormone

  Blood 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).

• Osteocalcin

  Serum 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).

• Calcium, Ionized

  Serum

  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).

• Calcium/Creatinine (mg/g)

  Urine 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).

• Phosphate/Creatinine (mg/g)

  Urine 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).

Study Arms (6)

Water

PLACEBO COMPARATOR

200 mL of water once a day for 14 days

Other: Placebo

Rifampin

ACTIVE COMPARATOR

Rifampin 600 mg once a day for 14 days

Drug: Rifampin

Grapefruit Juice

ACTIVE COMPARATOR

200 mL of grapefruit juice once a day for 14 days

Other: Grapefruit Juice

Grapefruit Juice Plus Rifampin

ACTIVE COMPARATOR

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

Drug: Rifampin; Other: Grapefruit Juice

Clarithromycin

ACTIVE COMPARATOR

Clarithromycin 250 mg twice a day for 14 days

Drug: Clarithromycin

Clarithromycin Plus Rifampin

ACTIVE COMPARATOR

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

Drug: Rifampin; Drug: Clarithromycin

Interventions

Rifampin DRUG

P450 inducer

Also known as: Rifadin

Clarithromycin Plus Rifampin; Grapefruit Juice Plus Rifampin; Rifampin

Clarithromycin DRUG

CYP3A4 and Pgp inhibitor in both intestine and liiver

Also known as: Biaxin

Clarithromycin; Clarithromycin Plus Rifampin

Grapefruit Juice OTHER

CYP3A4 inhibitor in intestine

Grapefruit Juice; Grapefruit Juice Plus Rifampin

Placebo OTHER

Water

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

MeSH Terms

Interventions

Rifampin; Clarithromycin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Limitations and Caveats

None noted

Results Point of Contact

• Title: Kenneth Thummel
• Organization: University of Washington

thummel@u.washington

206-543-0819

Study Officials

• Kenneth Thummel, Ph.D.

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Pharmaceutics

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: December 24, 2013
• Study Start: June 1, 2014
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: April 19, 2023
• Results First Posted: April 19, 2023

Record last verified: 2023-03

Locations

US (1)