RESUMO
Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child-Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49-1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45-1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51-1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.
RESUMO
BACKGROUND/AIMS: To evaluate the side effects of two antiplatelet agents - ticagrelor and eptifibatide - in mice with experimentally-induced inflammatory bowel disease. METHODS AND MATERIAL: This study was designed as a controlled, animal, drug safety investigation. C57Bl/6 mice were used to establish the ulcerative colitis model by exposure to dextran sulfate sodium (DSS), and divided into three experimental groups: eptifibatide-treated (150 µg/day intraperitoneally; n = 10), ticagrelol-treated (1 mg/day via gastric tube; n = 10), and DSS-control (plain drinking water; n = 10). An unmodeled non-DSS group served as the experimental control. Complete blood count was taken for all mice at baseline (day 0, treatment initiation) and after four days of treatment. On day 4, all animals were sacrificed for autopsy. The primary outcome measure was bleeding, and the secondary outcomes were change in platelet count, hemoglobin level, and hematocrit level. RESULTS: Neither ticagrelor nor eptifibatide treatment produced a significant effect on DSS colitis mice for the safety parameters measured. Platelet count and hemoglobin and hematocrit levels were statistically similar between the three DSS groups and the non-DSS control group (P > 0.05). Autopsy found no evidence of recent bleeding in liver, spleen, central nervous system or serous cavities. CONCLUSION: The antiplatelet agents ticagrelor and eptifibatide were safe in DSS colitis mice, suggesting their potential in humans suffering from ulcerative colitis, and supporting future safety studies.
