CORT125134 Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the dose-related safety, tolerability,
      pharmacokinetics (PK) and pharmacological effects (PD) of CORT125134 and its active
      metabolite CORT125201 after single and multiple ascending oral doses of CORT125134 in healthy
      participants.
    

Detailed description: 
      This is a 3-part, single-center study of single and multiple ascending doses of CORT125134 in
      healthy participants.

      Part I is a single dose study. Initially, participants will be enrolled sequentially into 1
      of up to 6 cohorts, each containing 10 participants, in a double-blind, randomized,
      placebo-controlled assessment of single-ascending doses (SAD) of CORT125134. Within each
      cohort, 8 participants will be randomly assigned to receive a single dose of CORT125134, and
      2 participants will be randomly assigned to receive a single dose of matching placebo.
      Thereafter, Cohort 7 will be a food-effect cohort, in which all 8 participants will receive a
      single dose of CORT125134 after a high-fat breakfast (open label). Cohorts 8 and 9 will be
      pharmacological effect cohorts, in each of which 10 participants will receive a challenge
      agent (prednisone, 25 mg) alone on Day -19; with an active comparator (mifepristone, 600 mg)
      on Day -12, and with CORT125134 on Day 1 in an open-label single sequence crossover design.
      Pharmacological effects will be explored by measuring effects on peripheral blood eosinophil,
      lymphocyte and neutrophil counts, serum osteocalcin, assay of messenger ribonucleic acid
      (mRNA) expression of FK506 Binding Protein 5 (FKBP5) and Glucocorticoid-induced Leucine
      Zipper (GILZ) in whole blood (proof of pharmacological effect Cohort 8) and by measuring
      effects on oral glucose tolerance (proof of concept Cohort 9).

      Part 2 and 3 will be double-blind, randomized, placebo-controlled assessments of multiple
      oral ascending doses (MAD) of CORT125134. Participants will be enrolled sequentially into 1
      of up to 4 cohorts (Cohorts 10-13), each containing 12 participants. Within each cohort, 9
      participants will be randomly assigned to receive CORT125134 and 3 participants to receive
      matching placebo daily for 14 days (Days 1-14). The effects of CORT125134 on response to
      prednisone challenge will be additionally explored in Cohorts 12 and 13 in a single sequence
      crossover, with prednisone being given alone on Day -5 and in combination with CORT125134 or
      placebo on Day 14.

      Throughout the study, routine safety tests and assessments of PK (CORT125134 and CORT125201)
      will be performed, and changes in serum cortisol and plasma adrenocorticotrophic hormone
      (ACTH) measured.
    

Intervention name(s): CORT125134; Matching Placebo of CORT125134; Mifepristone; Prednisone; Glucose
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Oral capsules; Placebo; Active comparator; Challenge agent
Intervention MeSH terms: Prednisone; Cortisone; Mifepristone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Glucocorticoid receptor; antagonist