A FIM Study to Assess Safety and Exposure of Inhaled Single Doses of AP301-A Specific ENaC Channel Activator for the Treatment of Acute Lung Injury
AP301 is an activator of ENaC‐mediated Na+ uptake for the treatment of pulmonary permeability edema in acute respiratory distress syndrome (ARDS). The purpose of this “first‐in‐man” study was to examine local and systemic safety and systemic exposure of ascending single doses of AP301, when inhaled...
Gespeichert in:
Veröffentlicht in: | Journal of clinical pharmacology 2014-03, Vol.54 (3), p.341-350 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | AP301 is an activator of ENaC‐mediated Na+ uptake for the treatment of pulmonary permeability edema in acute respiratory distress syndrome (ARDS). The purpose of this “first‐in‐man” study was to examine local and systemic safety and systemic exposure of ascending single doses of AP301, when inhaled by healthy male subjects. In a double‐blind, placebo‐controlled study, 48 healthy male subjects were randomized to 6 ascending dose groups (single doses up to 120 mg) of 8 subjects each (3:1 randomization of AP301: placebo). Serial assessments included spirometry, exhaled nitric oxide (eNO), vital signs, ECG, safety laboratory, adverse events (AE), and blood samples for the quantification of AP301 in plasma. Descriptive statistics was applied. All 48 subjects received treatment, and completed the study as per protocol. No serious, local (e.g., hoarseness, cough, bronchospasm), or dose‐limiting AEs were noted. None of the assessments indicated notable dose or time‐related alterations of safety outcomes. Observed AP301 systemic exposure levels were very low, with mean Cmax values of |
---|---|
ISSN: | 0091-2700 1552-4604 |
DOI: | 10.1002/jcph.203 |