ACTH-Independent Adrenal Cushing Syndrome, Somatic, ACTH-Independent Cushing Syndrome, Autonomous Cortisol Secretion (ACS)
Conditions
Keywords
Autonomous Cortisol secretion (ACS), ACTH-independent adrenal Cushing's syndrome (aCs), benign adrenal tumor
Brief 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.
Detailed description
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.
Interventions
DRUGSPI-62 dose
SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 2 of drug (2mg).
Sponsors
Sparrow Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \< 180 mmHg systolic or \> 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c at Week 6 | Baseline to week 6 | HbA1c change from baseline |
| Change in HbA1c at week 12 | Baseline to week 12 | HbA1c change from baseline |
Countries
Romania, United Kingdom, United States
Contacts
STUDY_CHAIRFrank Czerwiec, MD
Sparrow Pharmaceuticals
Outcome results
None listed