Endocrine Abstracts

Injected depot formulations of somatostatin peptide analogs are routinely used to treat acromegaly and neuroendocrine tumors (NETs). Paltusotine (CRN00808), a small molecule nonpeptide selective somatostatin receptor 2 (sst2) agonist, is being evaluated for efficacy and safety in patients with acromegaly. The current Phase 1 study (NCT04246749) was conducted in two Parts: In Part A, the absorption, metabolism, excretion, and mass balance of a single oral dose of 20 mg [14C]-pa...

CRN04894 is a potent, orally bioavailable nonpeptide that is a highly selective antagonist for melanocortin type 2 receptor (MC2R). This receptor is found exclusively in the adrenal cortex and is the primary mediator of adrenal activation. We report results from a randomized, double-blinded, placebo-controlled (6 active:3 placebo/cohort), multiple ascending dose (40, 60, and 80 mg) study in health volunteers evaluating safety, pharmacokinetics, and pharmacodynamics of oral, on...

Peptide long-acting somatostatin receptor ligands (SRLs) are a first line medical treatment for acromegaly but are not efficiently absorbed when delivered orally. Years of injections with SRLs are associated with variable dose delivery, injection site reactions, and excessive life burden. Paltusotine (CRN00808) is a nonpeptide small molecule somatostatin type 2 (sst2) receptor agonist with high oral bioavailability (70%) and a 42–50 hour terminal elimination half-life in...

Long-acting somatostatin receptor ligands (LA-SRLs) are a first line medical treatment for acromegaly but require monthly parenteral administration. Paltusotine (CRN00808) is a nonpeptide, small molecule somatostatin type 2 (SST2) receptor agonist with high oral bioavailability (70%), suitable for once daily, oral dosing. The recently reported results of the ACROBAT Edge study (NCT03789656) suggest that patients with acromegaly treated with injected SRLs can switch to once dai...

Paltusotine is a once-daily, oral selective nonpeptide somatostatin receptor type 2 (SST2) agonist, which is in clinical development for the treatment of acromegaly. Maintenance of insulin-like growth factor 1 (IGF-1) control and toleration was demonstrated in phase 2 studies evaluating paltusotine in biochemically controlled (IGF-1 ≤1xULN) [ACROBAT Evolve (NCT03792555)] and uncontrolled (1> IGF-1 ≤2.5xULN) [ACROBAT Edge (NCT03789656)] patients with acromegaly ...

Cushing’s disease (CD) and Ectopic ACTH syndrome (EAS) stem from excess circulating adrenocorticotropic hormone (ACTH) and resulting hypercortisolemia. In CD, excess ACTH is secreted from pituitary tumors, whereas excess ACTH in EAS arises from nonpituitary tumors. ACTH acts on the adrenal melanocortin type 2 (MC2) receptor to control the synthesis and secretion of adrenal hormones, including the stress hormone cortisol (corticosterone in rats) which accounts for the com...