Cushing's Syndrome I, Cushing Disease Due to Increased ACTH Secretion, Cortisol Excess, Cortisol; Hypersecretion, Cortisol Overproduction, Ectopic ACTH Secretion
Conditions
Keywords
Cushing's Syndrome, ACTH Secretion, Cushing's Disease, Excessive Cortisol secretion, Cortisol, ectopic CRH secretion
Brief summary
This is a randomized, placebo-controlled, study of SPI-62 in subjects with ACTH-dependent Cushing's syndrome caused by a non-adrenal tumor. Subjects will receive each of the following 2 treatments for 24 weeks: SPI-62 and matching placebo with the option of long-term extension.
Detailed description
This is a multicenter, randomized, placebo-controlled, Phase 2 study to evaluate the pharmacologic effect, efficacy, and safety of SPI-62 in subjects with ACTH-dependent Cushing's syndrome. Each subject who provides consent and meets all inclusion and exclusion criteria will participate in a screening period (Days -35 to -8), a baseline period (Days -7 to -1), and a treatment period (Day 1 of Week 1 to Day 168 ± 3 days of Week 24) and, the option of long-term extension. Subjects have the option to continue with the study on active study drug and return to the site every 3 months for blood tests and study drug dispensing. The visits may be conducted remotely if testing can be arranged.
Interventions
DRUGSPI-62
11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor
DRUGPlacebo
Inactive tablets identical to SPI-62 tablets
Sponsors
Sparrow Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Staggered parallel crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or non-menstruating female * 18 years or older * Active and consistent cortisol excess * Documented diagnosis of ACTH-dependent Cushing's syndrome including Cushing's disease, ectopic ACTH secretion, and ectopic CRH secretion.
Exclusion criteria
* Recent (within 6 weeks) surgery for Cushing's or surgery planned within 24 weeks of randomization. * History of any fractionated radiation therapy for Cushing's within the past 2 years or conventional radiation therapy within 4 years. * History of bilateral adrenalectomy or exogenous, pseudo, cyclic, or non-ACTH-dependent Cushing's syndrome (including certain inherited conditions). * High risk of acute morbidity from corticotroph adenoma growth (similar to that which occurs with Nelson's syndrome) defined as current evidence of macroadenoma at risk of impingement of vital structures. * Any current or prior medical condition, medical or surgical therapies, or clinical trial participation expected to interfere with the conduct of the study or the evaluation of its results, including but not limited to poor venous access or recent receipt or donation of blood products. * Women who are currently pregnant, lactating or planning fertility and unwilling to adhere to approved contraceptives or abstinence.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in urinary HSD-1 ratio | Baseline to 6 weeks | The urinary HSD-1 ratio (tetrahydrocortisol + allotetrahydrocortisol ) / tetrahydrocortisone will be used as a biomarker of HSD-1 activity in liver. The primary analysis will include only subjects with Cushing's disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment emergent adverse events | Baseline through 24 weeks of treatment | Adverse events including clinically significant abnormal values on clinical laboratory evaluations, continuous glucose monitoring (CGM), 12-lead ECGs, vital signs measurements (including orthostatic vital sign measurements), physical examinations, and HPA and HPG axis biomarkers |
Countries
Bulgaria, Romania, United States
Outcome results
None listed