Study in Healthy Subjects to Determine the Effect of Relacorilant on Exposure to Probe Substrates for Cytochrome P450s
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Midazolam hydrochloride; Metoprolol tartrate; Pioglitazone hydrochloride; Tolbutamide; Omeprazole; Relacorilant
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Midazolam hydrochloride 2.5 mg; Metoprolol tartrate 100 mg; Pioglitazone hydrochloride 15 mg; Tolbutamide 500 mg; Omeprazole 20 mg; Relacorilant 350mg
Other intervention name(s): Versed; Lopressor; Actos; Orinase; Prilosec; CORT125134
Intervention MeSH terms: Pioglitazone; Tolbutamide; Metoprolol; Midazolam; Omeprazole
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other