Two randomized, double-blind, placebo-controlled, dose-escalation phase 1 studies evaluating BTH1677, a 1, 3–1,6 beta glucan pathogen associated molecular pattern, in healthy volunteer subjects

摘要: Background BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of in healthy subjects are reported. Subjects Methods In Phase 1a single-dosing study, were randomized (3:1 per cohort) to single intravenous (iv) infusion at 0.5, 1, 2, 4, or 6 mg/kg placebo, respectively. 1b multi-dosing 7 daily iv infusions 4 mg/kg Safety PK non-compartmental analyses performed. Results Thirty-six (N = 24 1a; N = 12 1b) treatment. No deaths serious adverse events occurred either study. Mild moderate (AEs) 67 % BTH1677-treated both studies. Treatment-related AEs (occurring ≥10 % subjects) included dyspnea, flushing, headache, nausea, paraesthesia, rash conjunctivitis headache 1b. serum concentration was linear with dose. Clearance, elimination half-life (t1/2) volume distribution (Vss) dose-independent. 1b, area under curve, t1/2, Vss values larger steady state on days 6–30 versus day 0. Conclusions well tolerated after doses up 4 mg/kg.