spi-62 as a treatment for hypercortisolism related to a benign adrenal tumor

Conditions: Autonomous Cortisol Secretion (ACS); ACTH-Independent Cushing Syndrome; ACTH-Independent Adrenal Cushing Syndrome, Somatic

Summary: this is study with spi-62 to evaluate the efficacy, safety, and pharmacological effect of spi-62 in subjects with hypercortisolism related to a benign adrenal tumor. each subject will receive 2mg of spi-62 daily.

this is a multicenter, open-label, single-arm study, phase 2 study to estimate spi-62's effect on clinical features of hypercortisolism related to a benign adrenal tumor, including diabetes/impaired glucose tolerance, hyperlipidemia, hypertension, and osteopenia. each subject who provides consent and meets all inclusion and exclusion criteria will participate in a screening period and an open-ended treatment period. visits occur at screening/baseline, months 1, 3, 6, 9, and 12, and then quarter-annually.

Eligibility criteria:
inclusion criteria: diagnosis and main criteria for inclusion and exclusion: the following are the main inclusion criteria: * adults able to provide informed consent. * documented characteristically benign adrenal nodule, with diameter ≤ 4 cm, homogenous texture, and non-contrast computerized tomography ≤ 20 hu attenuation or proven to be non malignant. * diagnosis of diabetes mellitus, pre-diabetes or impaired glucose tolerance, either untreated or on stable standard of care treatment, based on at least one of: * hba1c ≥ 5.7% but not \> 9.5% * 2-hour glucose level ≥ 7.8 mmol (140 mg/dl) on a 75 g ogtt * at least one additional documented cortisol-related morbidities, either untreated or on stable standard of care treatment: * hypercholesterolemia with total cholesterol \> 3.9 mm (150 mg/dl); * hypertriglyceridemia with triglycerides \> 2.3 mm (200 mg/dl); * osteopenia with bone densitometry z-score \< -2.0 or t-score \< -1.0; * history or evidence of minimally traumatic or osteoporotic fracture; or * hypertension with resting supine blood pressure \> 130 but \ 85 but \< 120 mmhg diastolic. * poorly suppressible hypercortisolemia: * morning serum cortisol \> 50 nm (1.8 mcg/dl) after a 1 mg ondst. * subjects with dexamethasone \< 3.3 nmol/l (130 ng/dl) will undergo a high-dose (8 mg) ondst. * subjects who take estrogen-containing medicines will be evaluated based on free cortisol \> 2.2 nm (80 ng/dl). * for subjects with morning serum cortisol \> 138 nm (5.0 mcg/dl) after ondst, the investigator will assess for adrenal cushing's syndrome. exclusion criteria: * diagnosis of acth-dependent cushing's syndrome, pheochromocytoma, aldosteronoma, adrenocortical carcinoma, or congenital adrenal hyperplasia, or other malignancy associated hypercortisolism including history of adrenal carcinoma. * history of adrenalectomy or planned adrenalectomy within 4 months after randomization. * exogenous hypercortisolism. * uncontrolled, clinically significant hypo- or hyperthyroidism. * history of idiopathic thrombocytopenia. * moderately impaired renal function (estimated glomerular filtration rate \< 60 ml/min/1.73m2). * history of cancer (other than non-melanoma skin, thyroid, or early-stage prostate cancer) within 3 years. * any major surgery, or significant post-operative sequelae, within 1 month prior to informed consent or planned during the trial. * pregnant or lactating. * positive test for severe acute respiratory syndrome coronavirus 2 infection within 4 weeks, or hospitalization for coronavirus disease 2019 within 6 months, prior to randomization. * any other current or prior medical condition expected to interfere with the conduct of the trial or the evaluation of its results. * participation in any clinical trial within 3 months prior to the first dose of study drug, or longer depending on half-life of the investigational therapy.

Keywords: autonomous cortisol secretion (acs) acth-independent adrenal cushing's syndrome (acs) benign adrenal tumor