Trial Outcomes & Findings for CYP3A4 Activity and Mineral Homeostasis (NCT NCT02019875)
NCT ID: NCT02019875
Last Updated: 2023-04-19
Results Overview
Serum 1, 25(OH) D3 Vitamin D
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
92 participants
Primary outcome timeframe
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).
Results posted on
2023-04-19
Participant Flow
Participant milestones
| Measure |
Water
200 mL of water once a day for 14 days
Placebo
|
Rifampin
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
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
|
Clarithromycin
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
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
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
16
|
18
|
15
|
15
|
16
|
12
|
|
Overall Study
COMPLETED
|
14
|
16
|
15
|
14
|
15
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
0
|
1
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
CYP3A4 Activity and Mineral Homeostasis
Baseline characteristics by cohort
| Measure |
Water
n=14 Participants
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=16 Participants
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 Participants
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=14 Participants
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
|
Clarithromycin
n=15 Participants
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=11 Participants
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
|
Total
n=85 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
27.5 years
STANDARD_DEVIATION 6.6 • n=99 Participants
|
29.5 years
STANDARD_DEVIATION 8.3 • n=107 Participants
|
32.1 years
STANDARD_DEVIATION 11.1 • n=206 Participants
|
29.9 years
STANDARD_DEVIATION 9.1 • n=7 Participants
|
28.1 years
STANDARD_DEVIATION 9.3 • n=31 Participants
|
27.3 years
STANDARD_DEVIATION 8.0 • n=30 Participants
|
29.2 years
STANDARD_DEVIATION 8.8 • n=3 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
9 Participants
n=31 Participants
|
5 Participants
n=30 Participants
|
51 Participants
n=3 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=31 Participants
|
6 Participants
n=30 Participants
|
34 Participants
n=3 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
2 Participants
n=30 Participants
|
4 Participants
n=3 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
14 Participants
n=7 Participants
|
15 Participants
n=31 Participants
|
9 Participants
n=30 Participants
|
81 Participants
n=3 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
1 Participants
n=3 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
17 Participants
n=3 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
1 Participants
n=3 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
4 Participants
n=3 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
10 Participants
n=31 Participants
|
11 Participants
n=30 Participants
|
62 Participants
n=3 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
PRIMARY outcome
Timeframe: 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).Population: Comparison of treatment effect (end of treatment - baseline) between treatment groups.
Serum 1, 25(OH) D3 Vitamin D
Outcome measures
| Measure |
Water
n=14 Participants
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=16 Participants
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 Participants
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=14 Participants
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
|
Clarithromycin
n=15 Participants
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=11 Participants
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
|
|---|---|---|---|---|---|---|
|
1, 25(OH) D3 Vitamin D
|
3.2 pM
Interval -11.0 to 17.4
|
1.7 pM
Interval -12.0 to 15.4
|
3.7 pM
Interval -10.5 to 17.9
|
-3.3 pM
Interval -17.5 to 10.9
|
-4.7 pM
Interval -18.4 to 9.0
|
0.4 pM
Interval -15.7 to 16.4
|
PRIMARY outcome
Timeframe: 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).Population: Comparison of treatment effect (end of treatment - baseline) between treatment groups.
Serum 25(OH) D3 Vitamin D
Outcome measures
| Measure |
Water
n=14 Participants
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=16 Participants
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 Participants
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=14 Participants
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
|
Clarithromycin
n=15 Participants
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=11 Participants
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
|
|---|---|---|---|---|---|---|
|
25(OH) D3 Vitamin D
|
-3.1 nM
Interval -6.6 to 0.4
|
-4.3 nM
Interval -7.7 to -1.0
|
-1.3 nM
Interval -4.8 to 2.1
|
-1.6 nM
Interval -5.1 to 1.8
|
0.6 nM
Interval -2.8 to 3.9
|
-5.0 nM
Interval -8.9 to -1.1
|
PRIMARY outcome
Timeframe: 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).Population: Comparison of treatment effect (end of treatment - baseline) between treatment groups.
Blood Parathyroid Hormone
Outcome measures
| Measure |
Water
n=14 Participants
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=16 Participants
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 Participants
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=14 Participants
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
|
Clarithromycin
n=15 Participants
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=11 Participants
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
|
|---|---|---|---|---|---|---|
|
Parathyroid Hormone
|
0.3 pg/mL
Interval -7.9 to 8.4
|
0.4 pg/mL
Interval -7.2 to 8.1
|
1.6 pg/mL
Interval -6.3 to 9.5
|
1.0 pg/mL
Interval -7.2 to 9.1
|
2.7 pg/mL
Interval -5.2 to 10.6
|
0.6 pg/mL
Interval -8.6 to 9.8
|
PRIMARY outcome
Timeframe: 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).Population: Comparison of treatment effect (end of treatment - baseline) between treatment groups.
Serum Osteocalcin
Outcome measures
| Measure |
Water
n=14 Participants
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=16 Participants
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 Participants
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=14 Participants
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
|
Clarithromycin
n=15 Participants
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=11 Participants
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
|
|---|---|---|---|---|---|---|
|
Osteocalcin
|
0.0 ng/mL
Interval -1.1 to 1.2
|
-1.1 ng/mL
Interval -2.2 to 0.0
|
0.7 ng/mL
Interval -0.5 to 1.8
|
0.0 ng/mL
Interval -1.2 to 1.1
|
3.7 ng/mL
Interval 2.6 to 4.8
|
4.0 ng/mL
Interval 2.7 to 5.2
|
PRIMARY outcome
Timeframe: 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).Population: Comparison of treatment effect (end of treatment - baseline) between treatment groups.
Serum
Outcome measures
| Measure |
Water
n=14 Participants
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=16 Participants
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 Participants
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=14 Participants
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
|
Clarithromycin
n=15 Participants
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=11 Participants
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
|
|---|---|---|---|---|---|---|
|
Calcium, Ionized
|
0.0 mM
Interval -0.014 to 0.014
|
-0.008 mM
Interval -0.021 to 0.005
|
-0.017 mM
Interval -0.031 to -0.003
|
-0.011 mM
Interval -0.025 to 0.003
|
-0.005 mM
Interval -0.019 to 0.008
|
-0.009 mM
Interval -0.025 to 0.008
|
PRIMARY outcome
Timeframe: 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).Population: Comparison of treatment effect (end of treatment - baseline) between treatment groups.
Urine Calcium/Creatinine (mg/g)
Outcome measures
| Measure |
Water
n=14 Participants
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=16 Participants
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 Participants
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=14 Participants
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
|
Clarithromycin
n=15 Participants
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=11 Participants
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
|
|---|---|---|---|---|---|---|
|
Calcium/Creatinine (mg/g)
|
3.4 ratio (mg/g)
Interval -24.9 to 31.8
|
-9.2 ratio (mg/g)
Interval -36.5 to 18.2
|
-41.1 ratio (mg/g)
Interval -69.4 to -12.7
|
-3.8 ratio (mg/g)
Interval -32.1 to 24.5
|
6.3 ratio (mg/g)
Interval -21.1 to 33.6
|
41.4 ratio (mg/g)
Interval 9.5 to 73.3
|
PRIMARY outcome
Timeframe: 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).Population: Comparison of treatment effect (end of treatment - baseline) between treatment groups.
Urine Phosphate/Creatinine(mg/g)
Outcome measures
| Measure |
Water
n=14 Participants
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=16 Participants
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 Participants
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=14 Participants
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
|
Clarithromycin
n=15 Participants
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=11 Participants
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
|
|---|---|---|---|---|---|---|
|
Phosphate/Creatinine (mg/g)
|
8.3 ratio (mg/g)
Interval -69.0 to 85.5
|
11.1 ratio (mg/g)
Interval -63.5 to 85.7
|
23.3 ratio (mg/g)
Interval -54.0 to 100.5
|
79.6 ratio (mg/g)
Interval 2.3 to 156.8
|
5.5 ratio (mg/g)
Interval -69.1 to 80.1
|
60.0 ratio (mg/g)
Interval -27.1 to 147.1
|
Adverse Events
Water
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Rifampin
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Grapefruit Juice
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Grapefruit Juice Plus Rifampin
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Clarithromycin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Clarithromycin Plus Rifampin
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Water
n=16 participants at risk
200 mL of water once a day for 14 days
Placebo
|
Rifampin
n=18 participants at risk
Rifampin 600 mg once a day for 14 days
Rifampin: P450 inducer
|
Grapefruit Juice
n=15 participants at risk
200 mL of grapefruit juice once a day for 14 days
Grapefruit Juice: CYP3A4 inhibitor in intestine
|
Grapefruit Juice Plus Rifampin
n=15 participants at risk
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
|
Clarithromycin
n=16 participants at risk
Clarithromycin 250 mg twice a day for 14 days
Clarithromycin: CYP3A4 and Pgp inhibitor in both intestine and liiver
|
Clarithromycin Plus Rifampin
n=12 participants at risk
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
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/16 • 35 days
|
5.6%
1/18 • Number of events 1 • 35 days
|
0.00%
0/15 • 35 days
|
0.00%
0/15 • 35 days
|
0.00%
0/16 • 35 days
|
0.00%
0/12 • 35 days
|
|
Skin and subcutaneous tissue disorders
itching
|
0.00%
0/16 • 35 days
|
0.00%
0/18 • 35 days
|
0.00%
0/15 • 35 days
|
0.00%
0/15 • 35 days
|
0.00%
0/16 • 35 days
|
8.3%
1/12 • Number of events 1 • 35 days
|
|
Hepatobiliary disorders
elevated transaminase
|
6.2%
1/16 • Number of events 1 • 35 days
|
0.00%
0/18 • 35 days
|
0.00%
0/15 • 35 days
|
6.7%
1/15 • Number of events 1 • 35 days
|
0.00%
0/16 • 35 days
|
0.00%
0/12 • 35 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place