The safety and tolerability of ascending single doses of intravenously applied APG101 was examined in a randomized, double-blind, placebo-controlled, mono-centre 鈥渇irst in man鈥?dose escalation study in 34 healthy male volunteers. Pharmacokinetics and pharmacodynamics were also assessed.
The maximum serum concentration of 460 渭g/ml was achieved following 1 h infusion of the highest dose of 20 mg/kg. The systemic clearance was low (0.4 to 0.5 ml/h kg). Mean terminal elimination half-life was 12 to 15 days.
Two patients suffering from malignant glioma received APG101 intravenously under compassionate use conditions. They received doses ranging from 5 mg to 600 mg APG101. No adverse events and no clinical significant changes in laboratory parameters related to APG101 were reported. The presence of anti-drug-antibodies (ADA) was investigated and revealed no detectable levels of ADA.
Overall, single ascending doses of APG101 up to 20 mg/kg body weight (bw) administered as infusion over 1 h were considered as safe and well tolerated in healthy volunteers. After the application of multiple doses of 400 mg in two glioma patients, steady state for APG101 seemed to be reached. These results support further clinical evaluation of APG101 at a dose of 400 mg per week in glioblastoma patients.