First clinical trials of novel ENaC targeting therapy, SPX-101, in healthy volunteers and adults with cystic fibrosis.
Pulm Pharmacol Ther
; 58: 101819, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31302339
ABSTRACT
BACKGROUND:
ENaC inhibition has been investigated as a CF treatment; however, small molecule inhibitors of ENaC lack efficacy and/or have shown dose-limiting hyperkalemia. SPX-101 is a novel, investigational small peptide (SPLUNC1 mimetic) that regulates ENaC density with the potential for efficacy without systemic effects.METHODS:
Two trials are presented The first was a Phase 1, 2-part, randomized, double-blind, placebo-controlled, ascending-dose study of nebulized SPX-101 in healthy adults. Part 1 evaluated 4 single doses of SPX-101 ranging from 20 to 240â¯mg. Part 2 evaluated a 14-day regimen of SPX-101 at 4 doses of SPX-101 ranging from 10 to 120â¯mg BID. Pharmacokinetics, adverse events, spirometry, vital signs, electrocardiograms, pulse oximetry, and clinical laboratory values were assessed. The second trial was a tolerability-confirming, Phase 1b, open-label study conducted in 5 adult subjects with CF. Ascending doses of SPX-101 inhalation solution (10â¯mg-120â¯mg BID) were administered for 7 days. Safety was assessed as described above.RESULTS:
All 64 healthy volunteers (32 in each Part) completed the single and multiple dose study. SPX-101 was well tolerated with little/no systemic exposure and with no hyperkalemia. Adverse events were generally mild with reported respiratory events associated with the purported pharmacological activity of SPX-101. Tolerability of SPX-101 was similarly observed in adults with CF; all 5 subjects treated with SPX-101 completed the study.CONCLUSIONS:
SPX-101 was well-tolerated across a range of doses and had little/no systemic exposure in healthy adults and adults with CF, thus supporting further study in patients with CF. CLINICALTRIAL. GOV REGISTRATION NCT03056989.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fibrosis Quística
/
Bloqueadores del Canal de Sodio Epitelial
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Pulm Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá