CORT125281 Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This initial Phase I study will evaluate the dose-related safety and tolerability
      pharmacokinetics (PK) of CORT125281, and CORT125324 (active metabolite), and pharmacodynamics
      (PD) after single and multiple ascending oral doses of CORT125281 in healthy subjects.
    

Detailed description: 
      Separate single-and multiple-ascending dose (SAD and MAD) parts will be conducted. Throughout
      each part of the study, safety, pharmacological (PD) and PK effects will be assessed. Safety
      and tolerability will be assessed using adverse event (AE) monitoring, measurement of vital
      signs, recording 12-lead electrocardiogram (ECG), physical examination and clinical
      laboratory safety tests. Blood samples will be collected at intervals for assay of plasma
      concentration of CORT125281 and CORT125324.

      The SAD part of the study is double-blind, randomized and placebo-controlled with respect to
      CORT125281. Two cohorts, each of 9 subjects, will receive three sequential single doses of
      the investigational medicinal product (IMP), either CORT125281 at the assigned dose level or
      placebo, in a partial within-subject crossover manner. The starting dose is CORT125281, 40
      mg; the rules for determining later doses are detailed within the protocol. The PD effects of
      CORT125281 will be examined by testing its ability to ameliorate the pharmacological effects
      of a concomitantly administered dose of prednisone.

      The MAD part of the study will be double-blind, randomized, placebo-controlled and
      parallel-group with respect to CORT125281. Up to four cohorts of 8 subjects, randomized so
      that 6 receive CORT125281 and 2 receive placebo, will participate in the study, so that up to
      four dose levels of CORT125281 are studied in total. An exploratory assessment will be made
      of the effect of repeated doses of CORT125281 on exposure to pioglitazone, probe substrate
      for CYP2C8. Each subject will be admitted on Day-1 for baseline assessments. On Day1,
      subjects will receive a single oral dose of pioglitazone, 15mg. From Day3 to Day16 (14 days),
      subjects will be dosed daily with IMP (CORT125281 at the selected dose or placebo). On Day13,
      subjects will receive a second dose of pioglitazone, 15 mg.
    

Intervention name(s): CORT125281, 40mg, fasted; Prednisone 25mg, fasted; Placebo oral capsule, fasted; Pioglitazone 15mg Tablet; Placebo oral capsule, fed; Prednisone 25mg, fed; CORT125281, 120mg, fasted; CORT125281, 360mg, fasted; CORT125281, 720mg, fasted; CORT125281, 360mg, fed; CORT125281, 360mg; CORT125281, 120mg; CORT125281, 180mg; CORT125281, 240mg; CORT125281, 360mg; Placebo oral capsule; Placebo oral capsule; Placebo oral capsule
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): CORT125281 is supplied as capsules for oral dosing; Challenge Agent, Dose and Route of Administration:
Standard release 25 mg tablets, orally administered; Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered; Probe Substrate, Dose and Route of Administration:
15 Mg tablet, orally administered; Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered; Challenge Agent, Dose and Route of Administration:
Standard release 25 mg tablets, orally administered; CORT125281 is supplied as capsules for oral dosing; CORT125281 is supplied as capsules for oral dosing; CORT125281 is supplied as capsules for oral dosing; CORT125281 is supplied as capsules for oral dosing; CORT125281 is supplied as capsules for oral dosing twice, 12 hours apart, fasted (morning) and after evening meal; CORT125281 is supplied as capsules for oral dosing once daily; CORT125281 is supplied as capsules for oral dosing twice daily; CORT125281 is supplied as capsules for oral dosing twice daily; CORT125281 is supplied as capsules for oral dosing once daily; Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered twice, 12 hours apart, fasted (morning) and after evening meal; Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered, twice daily; Reference Therapy, Dose and Route of Administration:
Placebo capsule, orally administered, once daily
Intervention MeSH terms: Pioglitazone; Prednisone; Cortisone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Glucocorticoid receptor; antagonist