This is an open-label, single-sequence, 3-period crossover study conducted in healthy subjects. Eligible subjects will participate in a single treatment period, in which they will receive the following treatments: Day 1, single doses of midazolam and metoprolol; Day 2, single doses of pioglitazone, tolbutamide, and omeprazole; Days 5 to 17, daily doses of relacorilant; Day 14, single doses of midazolam and metoprolol (with relacorilant); and, Day 15, single doses of pioglitazone, tolbutamide, and omeprazole (with relacorilant).
This is an open-label, single-sequence, 3-period crossover study conducted in healthy subjects. Subjects will be screened for eligibility for the study within 21 days before the first dose of study drug based on entrance criteria specified in Section 4. Eligible subjects will participate in a single treatment period, in which they will receive the following treatments: * Day 1: single doses of midazolam and metoprolol * Day 2: single doses of pioglitazone, tolbutamide, and omeprazole * Days 5 to 17: daily doses of relacorilant * Day 14: single doses of midazolam and metoprolol (with relacorilant) * Day 15: single doses of pioglitazone, tolbutamide, and omeprazole (with relacorilant) Blood samples will be collected before dosing and at intervals up to 24 hours after each midazolam dose, up to 48 hours after each metoprolol, tolbutamide, and omeprazole dose, and up to 72 hours after each pioglitazone dose for assay of the respective probe substrates and relevant metabolites. Additional samples will be collected during the relacorilant dosing period for assay of relacorilant and metabolites to confirm exposure and at the beginning (before dosing on Day 5) and near the end (Day 14) of the relacorilant dosing period for assay for 4β-OH cholesterol, a biomarker for CYP induction. Safety and tolerability will be monitored using AEs, clinical laboratory evaluations, 12-lead ECG recordings, vital sign and pulse oximetry measurements, and physical examinations. Subjects will be admitted to the Clinical Research Unit (CRU) on the morning of Day -1 following an 8-hour fast for baseline assessments and will remain confined until completion of procedures, 72 hours after the last dose of probe substrate and 24 hours after the last dose of relacorilant. Subjects may leave the CRU after safety review on the morning of Day 18. Each subject will have a follow-up (FU) visit 14 ± 2 days after the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Midazolam hydrochloride 2.5 mg
Metoprolol tartrate 100 mg
Pioglitazone hydrochloride 15 mg
Celerion
Tempe, Arizona, United States
Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
Ratio of population geometric means (GMR) for Reference Day (following a single dose with each probe substrate given within a cocktail of probe substrates) and Test Day (following the same dose given to subjects after 10 or 11 days of daily dosing with relacorilant) areas under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
Time frame: predose to 96 hrs postdose
Area under plasma concentration-time curve extrapolated to infinity (AUCinf)
Ratio of population geometric means (GMR) for Reference Day (following a single dose with each probe substrate given within a cocktail of probe substrates) and Test Day (following the same dose given to subjects after 10 days of daily dosing with relacorilant) areas under plasma concentration-time curve extrapolated to infinity (AUCinf)
Time frame: predose to 96 hrs postdose
Maximum plasma concentration (Cmax)
Ratio of population geometric means (GMR) for Reference Day (following a single dose with each probe substrate given within a cocktail of probe substrates) and Test Day (following the same dose given to subjects after 10 days of daily dosing with relacorilant) maximum plasma concentration (Cmax).
Time frame: predose to 96 hrs postdose
Adverse Events
Safety and tolerability measure by number of subjects who experience adverse events
Time frame: up to 8 weeks
Safety Labs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Time frame: up to 8 weeks
ECGs
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Purpose
OTHER
Masking
NONE
Enrollment
27
Tolbutamide 500 mg
Omeprazole 20 mg
Relacorilant 350mg
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Time frame: up to 8 weeks
Vital Signs
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs
Time frame: up to 8 weeks
Physical Examinations
Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical exams
Time frame: up to 8 weeks