ECE2020 Audio ePoster Presentations Pituitary and Neuroendocrinology (217 abstracts)
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
Miklos Toth 1 , Murray Gordon 2 , Mirjana Doknic 3 , Emese Mezosi 4 , Harpal Randeva 5 , Tonya Marmon 6 , Kim Fowler 6 , Rosa Luo 6 , Michael Monahan 6 , Ajay Madan 6 , Chris Ferrara-Cook 6 , R. Scott Struthers 6 & Alan Krasner 6
1Semmelweis University, Budapest, Hungary; 2Allegheny General Hospital, Pittsburgh, United States; 3Clinical Centre of Serbia, Belgrade, Serbia; 4University of Pécs Medical School, Pécs, Hungary; 5University Hospital Coventry & Warwickshire, Coventry, United Kingdom; 6Crinetics Pharmaceuticals Inc, San Diego, United States
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 healthy volunteers, suitable for once daily dosing. We hypothesized that patients partially controlled on stable long-acting SRLs could successfully switch to once daily oral paltusotine while maintaining baseline IGF-1 levels. ACROBAT Edge (NCT03789656) is an ongoing open label, single-arm exploratory study to evaluate the safety and efficacy of paltusotine in patients with acromegaly who have not achieved normal IGF-1 levels with SRL monotherapy (group 1) or with a SRL in combination with a dopamine agonist (group 2). Additional exploratory subgroups, also eligible for enrollment in this trial, all have normal IGF-1 at baseline and include subjects treated with a SRL in combination with a dopamine agonist (group 3), pasireotide LAR monotherapy (group 4), or a SRL in combination with pegvisomant (group 5). The study schedule requires a final SRL injection to be administered 4 weeks prior to switching to paltusotine monotherapy for 13 weeks of dose titration, followed by a 4-week drug washout period. Change from baseline in IGF-1 to the completion of the 13-week dose titration period is the primary endpoint to be evaluated in a target sample size of 30 subjects in groups 1 and 2. The rise in IGF-1 during the wash out period is used to provide supportive evidence of efficacy. The IDS-iSYS assay calibrated to WHO recombinant reference standard 02/254 is used to measure IGF-1. Initial data available from the ACROBAT Edge study will be reported. This will include summary statistics for IGF-1 at baseline, completion of treatment period, and after washout. Safety data will also be summarized. To date, there have been no reported serious adverse events or treatment discontinuations due to adverse events. This data snapshot of open label data from ACROBAT Edge will provide important information in guiding clinical development of paltusotine for the treatment of acromegaly.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more