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| ID | Type | Description | Link |
|---|---|---|---|
| R01GM063666 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of General Medical Sciences (NIGMS) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Water | Placebo Comparator | 200 mL of water once a day for 14 days |
|
| Rifampin | Active Comparator | Rifampin 600 mg once a day for 14 days |
|
| Grapefruit Juice | Active Comparator | 200 mL of grapefruit juice once a day for 14 days |
|
| 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 |
|
| Clarithromycin | Active Comparator | Clarithromycin 250 mg twice a day for 14 days |
|
| Clarithromycin Plus Rifampin | Active Comparator | Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rifampin | Drug | P450 inducer |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kenneth Thummel, Ph.D. | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Washington | Seattle | Washington | 98195 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Water | 200 mL of water once a day for 14 days Placebo |
| FG001 | Rifampin | Rifampin 600 mg once a day for 14 days Rifampin: P450 inducer |
| FG002 | Grapefruit Juice | 200 mL of grapefruit juice once a day for 14 days Grapefruit Juice: CYP3A4 inhibitor in intestine |
| FG003 | 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 Rifampin: P450 inducer Grapefruit Juice: CYP3A4 inhibitor in intestine |
| FG004 | Clarithromycin | Clarithromycin 250 mg twice a day for 14 days Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver |
| FG005 | Clarithromycin Plus Rifampin | Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days Rifampin: P450 inducer Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Water | 200 mL of water once a day for 14 days Placebo |
| BG001 | Rifampin | Rifampin 600 mg once a day for 14 days Rifampin: P450 inducer |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 1, 25(OH) D3 Vitamin D | Serum 1, 25(OH) D3 Vitamin D | Comparison of treatment effect (end of treatment - baseline) between treatment groups. | Posted | Mean | 95% Confidence Interval | pM | 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). |
|
35 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Water | 200 mL of water once a day for 14 days Placebo | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
None noted
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kenneth Thummel | University of Washington | 206-543-0819 | thummel@u.washington |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 16, 2016 | Feb 21, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 16, 2016 | Mar 27, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012293 | Rifampin |
| D017291 | Clarithromycin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Clarithromycin | Drug | CYP3A4 and Pgp inhibitor in both intestine and liiver |
|
|
| Grapefruit Juice | Other | CYP3A4 inhibitor in intestine |
|
| Placebo | Other |
|
| 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). |
| BG002 | Grapefruit Juice | 200 mL of grapefruit juice once a day for 14 days Grapefruit Juice: CYP3A4 inhibitor in intestine |
| BG003 | 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 Rifampin: P450 inducer Grapefruit Juice: CYP3A4 inhibitor in intestine |
| BG004 | Clarithromycin | Clarithromycin 250 mg twice a day for 14 days Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver |
| BG005 | Clarithromycin Plus Rifampin | Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days Rifampin: P450 inducer Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 |
| Grapefruit Juice |
200 mL of grapefruit juice once a day for 14 days Grapefruit Juice: CYP3A4 inhibitor in intestine |
| OG003 | 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 Rifampin: P450 inducer Grapefruit Juice: CYP3A4 inhibitor in intestine |
| OG004 | Clarithromycin | Clarithromycin 250 mg twice a day for 14 days Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver |
| OG005 | Clarithromycin Plus Rifampin | Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days Rifampin: P450 inducer Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver |
|
|
|
| Primary | 25(OH) D3 Vitamin D | Serum 25(OH) D3 Vitamin D | Comparison of treatment effect (end of treatment - baseline) between treatment groups. | Posted | Mean | 95% Confidence Interval | nM | 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). |
|
|
|
|
| Primary | Parathyroid Hormone | Blood Parathyroid Hormone | Comparison of treatment effect (end of treatment - baseline) between treatment groups. | Posted | Mean | 95% Confidence Interval | pg/mL | 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). |
|
|
|
|
| Primary | Osteocalcin | Serum Osteocalcin | Comparison of treatment effect (end of treatment - baseline) between treatment groups. | Posted | Mean | 95% Confidence Interval | ng/mL | 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). |
|
|
|
|
| Primary | Calcium, Ionized | Serum | Comparison of treatment effect (end of treatment - baseline) between treatment groups. | Posted | Mean | 95% Confidence Interval | mM | 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). |
|
|
|
|
| Primary | Calcium/Creatinine (mg/g) | Urine Calcium/Creatinine (mg/g) | Comparison of treatment effect (end of treatment - baseline) between treatment groups. | Posted | Mean | 95% Confidence Interval | ratio (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). |
|
|
|
|
| Primary | Phosphate/Creatinine (mg/g) | Urine Phosphate/Creatinine(mg/g) | Comparison of treatment effect (end of treatment - baseline) between treatment groups. | Posted | Mean | 95% Confidence Interval | ratio (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). |
|
|
|
|
| 16 |
| 0 |
| 16 |
| 1 |
| 16 |
| EG001 | Rifampin | Rifampin 600 mg once a day for 14 days Rifampin: P450 inducer | 0 | 18 | 0 | 18 | 1 | 18 |
| EG002 | Grapefruit Juice | 200 mL of grapefruit juice once a day for 14 days Grapefruit Juice: CYP3A4 inhibitor in intestine | 0 | 15 | 0 | 15 | 0 | 15 |
| EG003 | 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 Rifampin: P450 inducer Grapefruit Juice: CYP3A4 inhibitor in intestine | 0 | 15 | 0 | 15 | 1 | 15 |
| EG004 | Clarithromycin | Clarithromycin 250 mg twice a day for 14 days Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver | 0 | 16 | 0 | 16 | 0 | 16 |
| EG005 | Clarithromycin Plus Rifampin | Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days Rifampin: P450 inducer Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver | 0 | 12 | 0 | 12 | 1 | 12 |
| itching | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| elevated transaminase | Hepatobiliary disorders | Non-systematic Assessment |
|
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| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| Mean Difference (Final Values) |
| 1.8 |
| 2-Sided |
| 95 |
| -3.1 |
| 6.7 |
| Superiority |
| Mixed Models Analysis | 0.559 | Mean Difference (Final Values) | 1.5 | 2-Sided | 95 | -3.4 | 6.4 | Superiority |
| Mixed Models Analysis | 0.138 | Mean Difference (Final Values) | 3.7 | 2-Sided | 95 | -1.2 | 8.5 | Superiority |
| Mixed Models Analysis | 0.477 | Mean Difference (Final Values) | -1.9 | 2-Sided | 95 | -7.1 | 3.3 | Superiority |
| Mean Difference (Final Values) |
| 1.4 |
| 2-Sided |
| 95 |
| -10.0 |
| 12.7 |
| Superiority |
| Mixed Models Analysis | 0.91 | Mean Difference (Final Values) | 0.7 | 2-Sided | 95 | -10.8 | 12.2 | Superiority |
| Mixed Models Analysis | 0.68 | Mean Difference (Final Values) | 2.4 | 2-Sided | 95 | -8.9 | 13.8 | Superiority |
| Mixed Models Analysis | 0.96 | Mean Difference (Final Values) | 0.3 | 2-Sided | 95 | -11.9 | 12.6 | Superiority |
| Mean Difference (Final Values) |
| 0.6 |
| 2-Sided |
| 95 |
| -1.0 |
| 2.2 |
| Superiority |
| Mixed Models Analysis | 0.94 | Mean Difference (Final Values) | -0.1 | 2-Sided | 95 | -1.7 | 1.6 | Superiority |
| Mixed Models Analysis | <0.0001 | Mean Difference (Final Values) | 3.7 | 2-Sided | 95 | 2.1 | 5.2 | Superiority |
| Mixed Models Analysis | <0.0001 | Mean Difference (Final Values) | 3.9 | 2-Sided | 95 | 2.2 | 5.6 | Superiority |
| Mean Difference (Final Values) |
| -0.017 |
| 2-Sided |
| 95 |
| -0.037 |
| 0.003 |
| Superiority |
| Mixed Models Analysis | 0.29 | Mean Difference (Final Values) | -0.011 | 2-Sided | 95 | -0.031 | 0.009 | Superiority |
| Mixed Models Analysis | 0.61 | Mean Difference (Final Values) | -0.005 | 2-Sided | 95 | -0.025 | 0.015 | Superiority |
| Mixed Models Analysis | 0.46 | Mean Difference (Final Values) | -0.008 | 2-Sided | 95 | -0.03 | 0.014 | Superiority |
| Mean Difference (Final Values) |
| -44.5 |
| 2-Sided |
| 95 |
| -84.5 |
| -4.5 |
| Superiority |
| Mixed Models Analysis | 0.72 | Mean Difference (Final Values) | -7.2 | 2-Sided | 95 | -47.3 | 32.8 | Superiority |
| Mixed Models Analysis | 0.89 | Mean Difference (Final Values) | 2.8 | 2-Sided | 95 | -36.6 | 42.2 | Superiority |
| Mixed Models Analysis | 0.08 | Mean Difference (Final Values) | 38.0 | 2-Sided | 95 | -4.7 | 80.6 | Superiority |
| Mean Difference (Final Values) |
| 15.0 |
| 2-Sided |
| 95 |
| -94.2 |
| 124.2 |
| Superiority |
| Mixed Models Analysis | 0.20 | Mean Difference (Final Values) | 71.3 | 2-Sided | 95 | -37.9 | 180.5 | Superiority |
| Mixed Models Analysis | 0.96 | Mean Difference (Final Values) | -2.7 | 2-Sided | 95 | -110.1 | 104.7 | Superiority |
| Mixed Models Analysis | 0.38 | Mean Difference (Final Values) | 51.8 | 2-Sided | 95 | -64.7 | 168.2 | Superiority |