Searchable abstracts of presentations at key conferences in endocrinology

ea0070aep627 | Pituitary and Neuroendocrinology | ECE2020

Absolute oral bioavailability and absorption, metabolism, excretion of [14C]-Labeled paltusotine (CRN00808), an orally bioavailable, nonpeptide, selective, somatostatin receptor 2 (sst2) biased agonist for the treatment of acromegaly

Madan Ajay , Luo Rosa , Ferrara-Cook Chris , Scott Struthers R. , van Marle Sjoerd , Krasner Alan

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...

ea0056gp177 | Parathyroid | ECE2018

Maintenance of key biochemical parameters with recombinant human parathyroid hormone (1-84) in patients with hypoparathyroidism: an analysis of a long-term, open-label, single-centre study

Krasner Alan , Cusano Natalie E , Rubin Mishaela R , Piccolo Rebecca , Bilezikian John P

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...

ea0086oc3.3 | Reproductive and Neuroendocrinology | SFEBES2022

Long-term efficacy and safety of oral, once-daily paltusotine treatment in acromegaly: Two-year interim results from the ACROBAT Advance study

Randeva Harpal , Gadelha Monica , Gordon Murray , Doknic Mirjana , Mezősi Emese , Toth Miklos , Boguszewski Cesar , Ferrara-Cook Christine , Casagrande Alessandra , Krasner Alan

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...

ea0086p344 | Neuroendocrinology and Pituitary | SFEBES2022

CRN04894: an oral, nonpeptide adrenocorticotropic hormone (ACTH) receptor antagonist decreases basal and stimulated cortisol secretion in healthy volunteers

Trainer Peter , Ferrara-Cook Christine , Ayala Alejandro , Luo Rosa , Miller Stephanie , Wang Yang , Hernandez-Illas Martha , Scott Struthers R. , Betz Stephen , Krasner Alan

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...

ea0041ep129b | Bone & Osteoporosis | ECE2016

Similarities in postsurgical vs nonsurgical patients with hypoparathyroidism: post hoc analysis from recombinant human parathyroid hormone (rhPTH[1-84], parathyroid hormone rDNA) REPLACE study

Brandi Maria Luisa , Bilezikian John P , Clarke Bart L , Fraser William , Krasner Alan , Lagast Hjalmar , Li Benjamin , Mannstadt Michael , Rejnmark Lars , Shoback Dolores M , Vokes Tamara J

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 ...

ea0070aep628 | Pituitary and Neuroendocrinology | ECE2020

Safety and IGF-1 levels with once daily oral sst2 agonist paltusotine (CRN00808) in acromegaly patients previously treated with peptide long-acting somatostatin receptor ligands: Initial data from the open label ACROBAT Edge phase 2 study

Toth Miklos , Gordon Murray , Doknic Mirjana , Mezosi Emese , Randeva Harpal , Marmon Tonya , Fowler Kim , Luo Rosa , Monahan Michael , Madan Ajay , Ferrara-Cook Chris , Scott Struthers R. , Krasner Alan

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...

ea0056oc3.4 | New insights in bone disorders | ECE2018

Renal function change in chronic hypoparathyroidism patients treated with recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) and in a historical control cohort treated with standard therapy

Chen Kristina , Rubin Mishaela , Mu Fan , Swallow Elyse , Zhao Jing , Wang Jessie , Krasner Alan , Sherry Nicole , Signorovitch James , Ketteler Markus , Bilezikian John

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...

ea0073oc15.4 | Oral Communications 15: Late Breaking | ECE2021

Identification of a dose range for once daily oral paltusotine in patients with acromegaly that maintains IGF-1 levels when switching from long-acting somatostatin receptor ligand therapy

Gordon Murray B. , Gadelha Monica , Toth Miklos , Doknic Mirjana , Mezosi Emese , Randeva Harpal , Marmon Tonya , Luo Rosa , Monahan Michael , Madan Ajay , Struthers Scott , Krasner Alan

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...

ea0077p80 | Neuroendocrinology and Pituitary | SFEBES2021

ACROBAT Advance: progress report on a study of long-term safety and efficacy of paltusotine for the treatment of acromegaly

Randeva Harpal , R . Gadelha Monica , Gordon Murray B. , Mezosi Emese , Doknic Mirjana , Toth Miklos , Boguszewski Cesar , Jochelson Theresa , Nichols Melissa , Luo Rosa , Madan Ajay , Ferrara-Cook Christine , Krasner Alan , Casagrande Alessandra , Scott Struthers R.

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 ...

ea0081oc4.6 | Oral Communications 4: Pituitary and Neuroendocrinology 1 | ECE2022

ACROBAT advance: once daily, oral paltusotine treatment maintained long-term igf-1 at levels previously achieved with injectable long-acting somatostatin receptor ligands (LA-SRLs)

Gadelha Monica R , Randeva Harpal , Gordon Murray B , Mezosi Emese , Doknic Mirjana , Toth Miklos , Boguszewski Cesar L , Nichols Melissa , Jochelson Theresa , Henley Scott , Patel Meenal , Mendez Debbie Koh , Ferrara-Cook Christine , Krasner Alan , Casagrande Alessandra , Struthers R Scott

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...