First-in-human Study in Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This initial Phase I study will evaluate the safety, tolerability, and pharmacokinetics (PK)
      of single and multiple ascending doses of CORT118335, the effect of concomitant
      administration with food on exposure to CORT118335, and its pharmacological effect in healthy
      subjects.
    

Detailed description: 
      This is a 5-part, single-center study of single and multiple ascending doses of CORT118335 in
      healthy subjects.

      Parts I and 4 of the study are double-blind, randomized, placebo-controlled assessments of
      single-ascending doses (SAD) of CORT118335. Subjects will be enrolled sequentially into 1 of
      up 8 cohorts (Part 1, Cohorts A to D [Cohorts E to G have been cancelled]; Part 4, Cohorts A
      to D), each containing 8 subjects. Within each cohort, 6 subjects will be randomly assigned
      to receive a single dose of CORT118335 and 2 subjects will be randomly assigned to receive a
      single dose of matching placebo.

      Part 2 Cohort A, food-effect, will be an open-label 2-way crossover study in one cohort of 12
      subjects, randomized in a 1:1 ratio to receive a single dose of CORT118335 once after an
      overnight fast and once after a high-fat breakfast or the alternate sequence, over 2 study
      periods separated by a washout of at least 7 days/5 half-lives.

      Part 2 Cohort B, PD cohort, will be a double-blind, randomized, placebo-controlled, 3-way
      cross-over study and will serve as proof of pharmacological effect (GR modulation) for
      CORT118335. Subjects will be randomized in a 1:1:1 ratio to receive placebo, and two dose
      levels of CORT118335 in one of three treatment sequences across 3 study periods separated by
      washouts of at least 7 days/5 half-lives. On each occasion, the ability of CORT118335 to
      ameliorate the pharmacological effects of a single dose of prednisone will be measured.

      Parts 3 and 5 are double-blind, randomized, placebo-controlled assessments of multiple oral
      ascending doses of CORT118335. Subjects will be enrolled sequentially into 1 of up to 4
      cohorts (Part 1 Cohort A [Cohorts B to D have been cancelled; Part 5 Cohorts A to C), each
      containing 12 subjects. Within each cohort, 9 subjects will be randomly assigned to receive
      CORT118335 and 3 subjects to receive matching placebo daily for 14 days.

      Different formulations of CORT118335 will be used in Parts 1, 2 and 3, and in Parts 4 and 5.
    

Intervention name(s): CORT118335, 25 mg; Prednisone Oral Tablet; Glucose; Placebo oral suspension; CORT118335, 75mg; CORT118335, 225mg; CORT118335, 675mg; CORT118335, 600mg; CORT118335, 630mg; CORT118335, 375mg; CORT118335, 100mg; CORT118335, 300mg; CORT118335, 900mg; CORT118335, 150mg; CORT118335, 1500mg; Placebo oral capsule; CORT118335, dose to be determined
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): CORT118335 is supplied as capsules for oral dosing; Challenge Agent, Dose and Route of Administration:
Standard release 1x20mg and 1x5mg (25mg total) dose, orally administered.; 75 g in 300 mL solution, orally administered; Reference Therapy, Dose and Route of Administration:
Placebo suspension, orally administered.; CORT118335 is supplied as capsules for oral dosing; CORT118335 is supplied as capsules for oral dosing; CORT118335 is supplied as capsules for oral dosing; CORT118335 is supplied as capsules for oral dosing; CORT118335 is supplied as capsules for oral dosing; CORT118335 is supplied as capsules for oral dosing; CORT118335 is supplied as a suspension for oral dosing; CORT118335 is supplied as a suspension for oral dosing; CORT118335 is supplied as a suspension for oral dosing; CORT118335 is supplied as a suspension for oral dosing; CORT118335 is supplied as a suspension for oral dosing; Placebo capsules, orally administered; CORT118335 is supplied as suspension for oral dosing
Intervention MeSH terms: Prednisone; Cortisone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The 5 study parts may not be conducted entirely sequentially provided that this is justified by PK and safety data obtained from completed cohorts. The first MAD cohort will not start until data are available from at least 2 SAD levels using the same formulation.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science