The purpose of this study is to evaluate the potential effect of bardoxolone methyl on the pharmacokinetics of digoxin and rosuvastatin and to assess the safety of the concomitant administration of bardoxolone methyl with digoxin or rosuvastatin.
Subjects in Cohort 1 will receive a single dose of digoxin (0.5 mg) on Study Day 1, an initial dose of bardoxolone methyl (60 mg) and a single dose of digoxin (0.5 mg) on Study Day 10, and once daily doses of bardoxolone methyl (20 mg) on Study Days 11 through 14. Subjects in Cohort 2 will receive a single dose of rosuvastatin (20 mg) on Study Day 1, an initial dose of bardoxolone methyl (60 mg) and a single dose of rosuvastatin (20 mg) on Study Day 10, and once daily doses of bardoxolone methyl (20 mg) on Study Days 11 through 14. All doses will be given in the morning under fasting conditions. Bardoxolone methyl and the probe substrates (digoxin, rosuvastatin) will be dosed at the same time. Confinement will begin on Study Day -1 (Study Day before the first dosing day) and end after the collection of the 216 hour blood samples and scheduled study procedures on Study Day 19.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
32
Oral, Day 1 and Day 10
Oral, Day 1 and Day 10
Spaulding Clinical Research, LLC
West Bend, Wisconsin, United States
Maximum observed concentration
For Digoxin and Rosuvastatin
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
Time to maximum observed concentration
For Digoxin and Rosuvastatin
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
Area under the plasma-concentration time-curve
For Digoxin and Rosuvastatin
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
Oral clearance
For Digoxin and Rosuvastatin
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
Terminal rate constant
For Digoxin and Rosuvastatin
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
Terminal half-life
For Digoxin and Rosuvastatin
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
Amount excreted in Urine
For Digoxin only
Time frame: 0-24, 24-48, 484-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216 hours post-dose
Fraction of the dose excreted in Urine
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For Digoxin only
Time frame: 0-24, 24-48, 484-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216 hours post-dose
Renal clearance
For Digoxin only
Time frame: 0-24, 24-48, 484-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216 hours post-dose
Number of patients with Adverse Events
Time frame: Approximately 1 year
Determination of concentration for Bardoxolone Methyl
Sample will be taken at 0 hours and 3 hours after dosing only on Study Days 10, 12 and 14
Time frame: 0 hours and 3 hours after dosing