Endocrine Abstracts

While it is generally acknowledged that hyperthyroidism and Paget's disease are states of increased bone turnover and that treatment reduces this, whether treatment entirely corrects or reverses abnormalities has not been established. A variety of biomarkers for bone formation which include serum levels of bone alkaline phosphatase (BAP), osteocalcin (OC) and amino terminal procollagen type 1N propeptide (PINP) and resorption biomarkers which include urinary excretion of deoxy...

GH deficiency (GHD) in adults shares several clinical features with syndromes of glucocorticoid excess. Many patients with GHD also receive glucocorticoid therapy. GH inhibits the generation of active glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), but the confounding effect of ACTH deficiency/ cortisol replacement therapy has not been evaluated.Aims: To assess corticosteroid exposure and metabolism and body composition in...

In contrast to bone formation biomarkers, reliable bone resorption biomarkers have not been available in serum. Recently, automated measurement of C-terminal cross-linking telopeptide of type I collagen (CTX-I), has been promoted as a reliable indicator of bone resorption. The objective of the study was to examine the correlation of CTX-I, with the traditional urinary markers, N-telopeptide of type I collagen (NTX-I) and deoxypyridinoline (DPD) in a series of patients with Pag...

Measurement of the various available bone formation and resorption markers provide insights into different aspects of the bone metabolism process. Interpretation of bone biomarkers in a clinical setting is complex. Analysis of formation markers including bone alkaline phosphatase, procollagen type 1 propeptide and intact osteocalcin and resorption markers including free deoxypyridinoline and N-terminal cross-linking telopeptide of type 1 collagen were performed. From the inter...

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...

BackgroundMPOWERED, a large phase 3 trial, assessed maintenance of response to oral octreotide capsules (OOC; MYCAPSSA) compared to injectable somatostatin receptor ligands (iSRLs) in patients with acromegaly who responded to OOC and iSRLs (octreotide or lanreotide). OOC were recently approved in the US for patients with acromegaly who responded to and tolerated iSRLs.MethodsEligibility criteria included age ...

BackgroundInjectable somatostatin receptor ligands (iSRLs) have been a mainstay in acromegaly treatment. Oral octreotide capsules (OOC; MYCAPSSA®) were recently approved in the USA. Results from the placebo-controlled CHIASMA OPTIMAL and open-label CH-ACM-01 studies showed an OOC safety profile consistent with that of iSRLs with no new or unexpected safety signals. Results of the MPOWERED trial have enabled a comparison of OOC safety and ...

BackgroundPatients with acromegaly may have high symptom burden. The phase 3 MPOWERED trial assessed control of acromegaly by oral octreotide capsules (OOC; MYCAPSSA®) in comparison to injectable somatostatin receptor ligands (iSRLs) in patients responding to both OOC and iSRLs. iSRLs have been first-line medical treatment for patients with acromegaly for decades. OOC are newly approved in the US for patients previously controlled on iSRL...