MON-163 A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of a Selective Glucocorticoid Receptor Modulator, Relacorilant, in Patients with Autonomous Cortisol Secretion Due to Cortisol-Secreting Adrenal Adenoma(s)/Hyperplasia

Relacorilant is a highly selective glucocorticoid receptor antagonist that modulates the effects of excess cortisol without interacting with the mineralocorticoid or progesterone receptor. A Phase 2 relacorilant study in patients with endogenous Cushing syndrome (CS) demonstrated improvements in glycemic control and hypertension with no instances of drug-related hypokalemia or antiprogesterone effects. An international, multicenter, Phase 3 clinical trial of relacorilant is currently underway to evaluate the efficacy and safety of relacorilant in CS of various etiologies with evidence of hypercortisolism documented through two independent biochemical tests and at least two clinical signs and symptoms of CS. It uses a randomized-withdrawal design after 22-weeks (22wk) of open-label treatment with relacorilant (GRACE Study: NCT03697109). Here we introduce a double-blind, randomized, placebo-controlled study in patients with less severe CS secondary to adrenal adenoma(s) or hyperplasia. Approximately 130 eligible patients 18-80 years old with a radiologically confirmed adrenal lesion, a biochemical diagnosis of autonomous cortisol secretion and either impaired glucose tolerance/diabetes mellitus (IGT/DM) or hypertension will receive relacorilant (100 mg/day, titrated to 400 mg/day, as tolerated) or placebo over 22WK. Biochemical criteria for entry into the study include a serum cortisol >1.8 µg/dL after dexamethasone suppression testing (DST) and low (<10 pg/dL) or suppressed morning ACTH levels. Patients must be stable on their antidiabetic and/or antihypertensive agents for at least 4 weeks prior to the first dose of relacorilant. The primary efficacy endpoints are the between-treatment difference in change from Baseline to 22wk in AUCglucose for the IGT/DM group and mean systolic blood pressure (based on ambulatory blood pressure monitoring) for the hypertension group. Secondary endpoints include changes in weight, waist circumference, quality of life and coagulation markers. The safety analysis will be performed for all patients who received at least one dose of study drug. This will be the first randomized, double-blind, placebo-controlled study to test if patients with adrenal autonomous hypercortisolism benefit from medical treatment.