217. A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of the Lipopeptide QPX9003 in Healthy Adult Subjects. (15th December 2022) - Griffith, David
Abstract: Background: QPX9003 is a fully synthetic lipopeptide with potent activity against MDR Pseudomonas and Acinetobacter spp. This report describes the safety and pharmacokinetics of QPX9003 following single and multiple doses. Methods: Twelve healthy subjects were enrolled in 2 cohorts of up to 8 subjects (each cohort randomized to have up to 6 active and 2 placebo) each in the multiple ascending dose phase (100 or 200 mg every 6 hrs). Subjects received a single dose of QPX9003 followed by 48 hours of washout, then were administered QPX9003 q6h for 7 days. All infusions were administered over 1 hour. Intensive plasma sampling was obtained after dosing and assayed for QPX9003 content using validated HPLC/MS methods. Results: Single and multiple dose QPX9003 pharmacokinetic parameters (mean +/- SD) are shown below: Parameter Single Dose Last Dose of MD Single Dose Last Dose of MD 100 mg 100 mg q6h 200 mg 200 mg q6h N = 6 N = 6 N = 6 N = 5 Cmax (mg/L) 5.9 ± 1.1 8.1 ± 1.0 12.6 ± 3.0 18.3 ± 4.2 AUC0-6 (mg·h/L) 17.7 ± 3.0 29.0 ± 4.5 36.3 ± 8.9 62.2 ± 15.8 AUC0-inf (mg·h/L) 27.4 ± 6.0 NA 51.4 ± 12.0 NA Clearance (L/h) 3.8 ± 0.9 3.5 ± 0.6 4.1 ± 1.0 3.4 ± 1.0 Vss (L) 19.5 ± 3.4 24.2 ± 3.1 17.8 ± 4.6 20.8 ± 4.7 Half-Life (h) 4.5 ± 0.9 7.4 ± 1.4 4.1 ± 1.2 7.6 ± 0.9 No subjects discontinued due to AEs and no SAEs were observed. There was no evidence of increasing numbers or severity of AEs with increasing dose, and all AEs were mild or moderate in severity. Conclusion: QPX9003 was safe and well tolerated at all doses tested. QPX9003 plasma AUC and Cmax increased with increasing dose. QPX9003 plasma exposure accumulated ∼ 1.5 fold over 7 days of q6h dosing consistent with its plasma half-life. Based on the PK and safety profile, QPX9003 produces plasma exposures that exceed the PK-PD target safely and warrants further clinical development. Disclosures: David Griffith, n/a, Qpex Biopharma: Employee Yehuda Carmeli, MD, Allecra Therapeutics: Advisor/Consultant|MSD: Advisor/Consultant|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex Pharmaceuticals: Advisor/Consultant|Roche: Advisor/Consultant|Shinogi: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant Shawnee Gehrke, n/a, Qpex Biopharma: Employee Elizabeth Morgan, n/a, Qpex Biopharma: Employee Michael Dudley, n/a, ArrePath: Board Member|Qpex Biopharma: Board Member|Qpex Biopharma: Employee Jeff Loutit, MBChB, Qpex Biopharma: Employee.