Prophylactic treatment of bleeding episodes in children <12 years with moderate to severe hereditary factor X deficiency (FXD): Efficacy and safety of a high-purity plasma-derived factor X (pdFX) concentrate.

BACKGROUND: Hereditary factor X (FX) deficiency (FXD) affects 1:500 000-1:1 000 000 people worldwide. A novel, high-purity plasma-derived FX concentrate (pdFX) is available in the United States and European Union as replacement therapy for FXD, but data are scarce on pdFX use in children <12 years. AIM: This prospective, open-label phase 3 study assessed the safety, efficacy and pharmacokinetics of pdFX in children <12 years with moderate/severe FXD. METHODS: Subjects aged <12 years with basal plasma FX activity (FX:C) <5 IU/dL received pdFX as prophylactic and on-demand treatment, with doses adjusted to maintain FX:C > 5 IU/dL. After ≥26 weeks and ≥50 exposure days, investigators rated pdFX efficacy for preventing/decreasing bleeds. Secondary endpoints included number and severity of bleeds, trough FX:C and incremental recovery. Safety parameters were adverse events (AEs), inhibitor development and changes in laboratory parameters. RESULTS: The study enrolled 9 subjects (0-5 years, n = 4; 6-11 years, n = 5) with severe (n = 8) or moderate (n = 1) FXD. At end of study, investigators rated pdFX efficacy excellent for all subjects. Ten bleeds occurred (n = 3 subjects; 6 major, 3 minor, 1 unassessed for severity). Trough FX:C levels remained >5 IU/dL for all subjects after the last dose adjustment study visit. Mean incremental recovery was significantly lower for younger vs older subjects (1.53 vs 1.91 IU/dL per IU/kg; P = .001). All AEs were unrelated to treatment; no inhibitor development or clinically significant changes in laboratory parameters were observed. CONCLUSIONS: These results demonstrate the efficacy and safety of pdFX for treating children <12 years with moderate/severe hereditary FXD.

Diazepam and nicotine increase social interaction in gerbils: a test for anxiolytic action.

The effects of two drugs with anxiolytic actions, diazepam (0.1, 0.3 and 1 mg/kg) and nicotine (0.1 and 0.5 mg/kg) were examined on the time spent in social interaction by pairs of male gerbils. In a test arena lit by high light, diazepam (0.1 mg/kg) increased social interaction, without changing locomotor activity. Diazepam (0.3 and 1 mg/kg) produced a dose-related increase in locomotor activity, which reached significance at the higher dose. Nicotine produced a dose-related increase in social interaction, which reached significance at 0.5 mg/kg, but was without effect on locomotor activity. The specific increases in social interaction observed with diazepam and nicotine are similar to those seen in the well-validated social interaction test of anxiety in rats and suggest that social interaction in gerbils may also be used to screen for anxiolytic action of novel compounds.