Paltusotine, a novel oral once-daily nonpeptide SST2 receptor agonist, suppresses GH and IGF-1 in healthy volunteers.
Pituitary
; 25(2): 328-339, 2022 Apr.
Article
em En
| MEDLINE
| ID: mdl-35000098
ABSTRACT
PURPOSE:
Evaluate the pharmacodynamics, pharmacokinetics, and safety of paltusotine, an orally bioavailable, nonpeptide, somatostatin receptor subtype 2 (SST2) agonist being developed for the treatment of acromegaly and neuroendocrine tumors.METHODS:
A randomized, double-blind, placebo-controlled, single center, single and multiple ascending dose phase 1 study was conducted in healthy male volunteers who received (i) single-dose of oral paltusotine 1.25, 2.5, 5, 10, and 20 mg (solution); and 40 and 60 mg (capsules) or (ii) multiple-dose oral paltusotine capsules once daily 5 mg (× 7 days), 10, 20, and 30 mg (× 10 days). Main outcome measures were pharmacodynamics (changes in growth hormone-releasing hormone [GHRH] stimulated growth hormone [GH] and insulin-like growth factor 1 [IGF-1]), pharmacokinetics, safety, and tolerability.RESULTS:
Single-dose cohorts n = 41 active, n = 14 placebo. Multiple-dose cohorts n = 24 active, n = 12 placebo. Paltusotine was well tolerated, orally bioavailable, associated with increased plasma concentrations to doses up to 40 mg, and was eliminated with a half-life of approximately 30 h. Single-dose paltusotine 1.25 to 20 mg suppressed GHRH-stimulated GH secretion by 44% to 93% compared to 15% with placebo. Multiple-dose paltusotine 5 to 30 mg administered once daily for 10 days suppressed IGF-1 by 19% to 37% compared to an increase of 2.4% with placebo.CONCLUSIONS:
Paltusotine suppresses GH and IGF-1 in a dose-dependent fashion, with a safety profile similar to currently approved SST2 receptor ligands. Paltusotine is a promising once-daily oral nonpeptide SST2 agonist candidate for managing acromegaly and neuroendocrine tumors. TRIAL REGISTRATION NCT03276858, registered September 8, 2017, retrospectively registered.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acromegalia
/
Hormônio do Crescimento Humano
Tipo de estudo:
Clinical_trials
Limite:
Humans
/
Male
Idioma:
En
Revista:
Pituitary
Ano de publicação:
2022
Tipo de documento:
Article