A Phase 3 Study of the Efficacy and Safety of Relacorilant

• In patients with DM/IGT, the proportion of patients who meet any of the DM/IGT response criteria at the end of the OL phase (Week OL22).[ Time Frame: Open Label Phase (Baseline to Week OL22) ]
  - The DM/IGT response criteria for the Open-Label Phase (assessed at Week OL22) are: HbA1c has decreased by ≥0.5% from Baseline The 2-hour oGTT glucose is normalized (<140 mg/dL) or decreased by ≥50 mg/dL from Baseline Total daily insulin dose has decreased by ≥25% or daily sulfonylurea dose has decreased from Baseline by ≥50% and HbA1c is unchanged or decreased compared with Baseline
• In patients with hypertension, the proportion of patients who meet any of the hypertension response criteria at the end of the OL phase (Week OL22)[ Time Frame: Open Label Phase (Baseline to Week OL22) ]
  The hypertension response criteria for the Open-Label Phase (assessed at Week OL22) are: ≥5 mm Hg decrease in SBP and/or DBP from Baseline without worsening of either, based on 24-hour ABPM A reduction in the number or dose of BP medications, and SBP and DBP by ABPM are no worse than at Baseline.
• The mean change from Baseline to Week OL22 in Cushing Quality-of-Life (QoL) score[ Time Frame: Open Label Phase (Baseline to Week OL22) ]
  The Cushing Quality of Life (QoL) patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome (Webb et al. 2008), will be administered to all patients. It comprises 12 questions, each with 5 possible answers. The total score ranges from 12‒60. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns. Lower values reflect lower quality of life.
• Proportion of patients who worsened, as assessed by the Global Clinical Response, from Week OL22 to Week RW12/ET[ Time Frame: Week OL22 to Week RW12 ]
  Global Clinical Response will be scored in 7 categories: glucose, blood pressure, body composition, clinical appearance, strength, psychiatric health/ cognitive function, Cushing QoL score. An independent Data Review Board (DRB) will review the 7 categories of clinical parameters above to evaluate whether a patient's signs and symptoms of Cushing syndrome have changed and will rate each patient's overall response based on the totality of signs and symptoms as +1 (improved), 0 (unchanged), or −1 (worsened) at every visit after Baseline. Each patient's final score will be the median of the 3 ratings

This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess the safety and efficacy of relacorilant in patients with endogenous Cushing syndrome and concurrent 1) Type 2 diabetes mellitus/impaired glucose tolerance and/or 2) uncontrolled hypertension

• Drug: Relacorilant
  Relacorilant is supplied as 100 mg capsules for oral dosing.
• Other: Placebo
  Placebo matched to study drug

• Experimental: Relacorilant (open-label phase)
  The dose of relacorilant will be increased sequentially from 100 mg orally once daily to a target dose of 400 mg once daily.
• Experimental: Relacorilant (randomized-withdrawal phase)
  Patients who meet any of the response criteria will advance to the randomized-withdrawal phase of the study and receive the same highest dose as in the open-label phase.
• Placebo Comparator: Placebo (randomized-withdrawal phase)
  Placebo matched to study drug