Abstract
Purpose :
Limitations and gaps in current treatments such as laser photocoagulation, anti-vascular endothelial growth factor (VEGF), and steroid therapy underscore the need for new options for patients with DME. CU06-1004 (CU06) is a novel, orally administered vascular leakage blocker that was confirmed to inhibit angiogenesis and stabilize vessels in an oxygen-induced retinopathy mouse model and a laser-induced CNV (Choroidal neovascularization) beagle dog model and is in development for the treatment of DME. This study is a first-in-human, phase 1 dose escalation study to evaluate the safety, tolerability, and pharmacokinetics (PK) of CU06.
Methods :
This phase 1 study is a randomized, double-blind, placebo-controlled investigation of single (SAD) and multiple ascending dose (MAD). The study was performed on a total of 80 healthy subjects (male or female, 19-55 years of age) at a dose ranging between 100 and 1200 mg once daily or twice daily for up to 7 days. The food-effect bioavailability was also assessed by comparing PK parameters under fed versus fasting conditions.
Results :
Across the dose range CU06 100 mg to 1200 mg the increase in AUC0-t and Cmax with an increase in dose was more than dose proportional. No noticeable accumulation of CU06 was observed in either SAD or MAD. All urine samples in all subjects were below the limit of quantitation for each analyte. The administration of food increased exposure of CU06 and its metabolites. After single 300 mg (fasted) and 200 mg (fed) CU06, based on dose-normalized exposure parameters, DN (Dose-normalized) AUC0-t and DN Cmax, exposure to CU06 under fed conditions was 22.2- and 20.4-fold higher compared to fasted, respectively. There were no deaths, serious adverse events (SAEs), or subject discontinuations due to AEs.
Conclusions :
Ascending single and multiple doses of CU06 appeared to be safe and generally well tolerated by the subjects in this study. There was a substantial food effect on CU06 and its metabolites. CU06 is currently in phase 2a trial in the USA and top-line data from the trial are expected in the first half of 2024. CU06 could be a potential oral therapy for the treatment of DME.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.