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...

Hypoparathyroidism is a rare disorder characterised by hypocalcaemia and insufficient or undetectable parathyroid hormone (PTH). Recombinant human PTH, rhPTH(1-84), has been approved in the United States and Europe as an adjunctive treatment for adult patients with hypoparathyroidism. When hypoparathyroidism is established, long-term administration of rhPTH(1-84) is a treatment option. Thus, long-term safety and efficacy data for rhPTH(1-84) are needed. To this end, we evaluat...

Paltusotine is an investigational oral, once-daily, non-peptide, SST2 agonist in development for the treatment of acromegaly and neuroendocrine tumors. Interim analysis results from subjects with acromegaly treated with paltusotine for up to 2 years in ACROBAT Advance (NCT04261712), an ongoing, open-label extension study are reported here. Prior to Advance, subjects previously completed one of two Phase 2 parent studies, Evolve (NCT03792555, with normal IGF-1 using injected lo...

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...

Hypoparathyroidism, a rare disorder characterized by absent or low levels of parathyroid hormone (PTH), often results from thyroid surgery. However, nonsurgical etiologies are present in >10% of patients. Data about this group of patients are limited.In this post hoc REPLACE (NCT00732615, EudraCT2008-005063-34) analysis, baseline characteristics and response to 50–100 μg/day rhPTH(1-84) in patients with postsurgical or nonsurgical ...

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...

Standard therapy (ST) for chronic hypoparathyroidism (HPT) includes calcium and active vitamin D supplementation, which can be associated with an increased risk of renal complications. This study compared renal function change, assessed by estimated glomerular filtration rate (eGFR) over 5 years between HPT patients receiving rhPTH1-84 as an adjunct to ST and a historical control cohort without rhPTH1-84. rhPTH1-84-treated HPT patients were selected from two single-arm, long-t...

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 ...

Paltusotine is a once-daily, oral, nonpeptide somatostatin receptor type 2 (SST2) specific agonist, in development for the treatment of acromegaly and neuroendocrine tumors. We report interim results from ACROBAT Advance (NCT04261712), an ongoing, multicenter, open-label, long-term extension study of paltusotine in subjects with acromegaly who previously completed either Phase 2 study ACROBAT Edge (NCT03789656) or Evolve (NCT03792555). ACROBAT Edge enrolled 47 subjects with el...