Hypercortisolism Related to a Benign Adrenal Tumor MedDRA version: 22.1 Level: LLT Classification code 10020611 Term: Hypercortisolism System Organ Class: 100000004860
Conditions
Interventions
Product Name: SPI-62
Product Code: SPI-62
Pharmaceutical Form: Tablet
INN or Proposed INN: Not applicable
CAS Number: 1204178-50-6
Current Sponsor code: SPI-62
Other descriptive name: SPI-62
Concentra
Sponsors
Sparrow Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The following are the main inclusion criteria: • Adults able to provide informed consent. • Documented characteristically benign adrenal nodule(s), either unilateral or bilateral, with a maximum individual diameter = 4 cm, homogenous texture, and non-contrast computerized tomography = 20 HU attenuation or proven to be non-malignant. Subjects with adenoma attenuation between 11 to 20 HU, inclusive, must have had adequate evaluation to exclude pheochromocytoma prior to performing the ONDST. • Diagnosis of type 2 diabetes mellitus (excluding newly diagnosed subjects with less than 6 weeks of standard of care therapy and poorly controlled subjects), prediabetes or impaired glucose tolerance, either untreated or on stable standard of care treatment, based on at least one of: o HbA1c = 5.7% but not > 9.5% o 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: o hypercholesterolemia with total cholesterol > 3.9 mM (150 mg/dL); o hypertriglyceridemia with triglycerides > 2.3 mM (200 mg/dL); o osteopenia with bone densitometry Z-score 130 but 85 but 50 nM (1.8 mcg/dL) after a 1 mg ONDST. o Subjects who are incompletely suppressed, but with dexamethasone 138 nM (5.0 mcg/dL) after ONDST, must have the Investigator’s clinical classification as having either a diagnosis of ACS or aCs. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 105 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: The following are the main exclusion criteria: • Diagnosis of ACTH-dependent Cushing's syndrome, pheochromocytoma, aldosterinoma, 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 (abnormal TSH values are acceptable as long as the free T4 values are within the normal range). • 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 SARS-CoV-2 active, transmissible infection within 4 weeks, or hospitalization for SARS-CoV-2 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. • Diagnosis or biochemical evidence of aldosterinoma (unless co-secreting with cortisol and non-hypertensive or otherwise ineligible for, or unwilling to receive adrenalectomy). • Evidence of inadequately treated hepatitis B (HBsAg positive) or C (hepatitis C antibody positive unless viral load adequately suppressed).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is: • 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; ;Secondary Objective: The secondary objectives of this study are: • to evaluate the safety of SPI-62 in patients with hypercortisolism related to a benign adrenal tumor, including changes on HPA and HPG axis biomarkers and associated AEs; and • to assess the pharmacological effect of SPI-62 on hepatocellular cortisol/cortisone equilibrium in patients with hypercortisolism related to a benign adrenal tumor.;Primary end point(s): Primary endpoint is: Efficacy: 1. Glycemic control ;Timepoint(s) of evaluation of this end point: Efficacy: 1.change from baseline at Week 12; | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: 1. Hyperlipidemia 2. Hypertension 3. Osteopenia Safety: • AEs. • Clinical laboratory evaluations • 12-lead ECGs. • Vital sign measurements Pharmacologic: • Effect of SPI-62 on hepatocellular cortisol and cortisone Pharmacokinetic: • Amounts of SPI-62 and its metabolite AS2570469 excreted in urine (over 24 hours) and remaining in blood will be reported. ;Timepoint(s) of evaluation of this end point: Efficacy: 1. change from baseline at Week 12; 2. change from baseline at Week 12; 3. change from baseline at Week 12; Safety: Throughout the study Pharmacologic: • change from baseline at Week 12; Pharmacokinetic: • Throughout the study | — |
Countries
Bulgaria, France, Germany, Italy, Romania, United States
Contacts
Public ContactFrank Czerwiec
Sparrow Pharmaceuticals, Inc.
Outcome results
None listed