title: 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.
abstract: BACKGROUND
  BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported.
  
  
  METHODS
  In the Phase 1a single-dosing study, subjects were randomized (3:1 per cohort) to a single intravenous (i.v.) infusion of BTH1677 at 0.5, 1, 2, 4, or 6 mg/kg or placebo, respectively. In the Phase 1b multi-dosing study, subjects were randomized (3:1 per cohort) to 7 daily i.v. infusions of BTH1677 at 1, 2, or 4 mg/kg or placebo, respectively. Safety and PK non-compartmental analyses were performed.
  
  
  RESULTS
  Thirty-six subjects (N = 24 Phase 1a; N = 12 Phase 1b) were randomized to treatment. No deaths or serious adverse events occurred in either study. Mild or moderate adverse events (AEs) occurred in 67% of BTH1677-treated subjects in both studies. Treatment-related AEs (occurring in ≥10% of subjects) included dyspnea, flushing, headache, nausea, paraesthesia, and rash in Phase 1a and conjunctivitis and headache in Phase 1b. BTH1677 serum concentration was linear with dose. Clearance, serum elimination half-life (t1/2) and volume of distribution (Vss) were BTH1677 dose-independent. In Phase 1b, area under the curve, t1/2, and Vss values were larger at steady state on days 6-30 versus day 0.
  
  
  CONCLUSIONS
  BTH1677 was well tolerated after single doses up to 6 mg/kg and after 7 daily doses up to 4 mg/kg.
authors: Prism Research, 1000 Westgate Drive, St. Paul, MN, 55114, USA.
authors: C E
authors: CE
authors: Halstenson
authors: Prism Research, 1000 Westgate Drive, St. Paul, MN, 55114, USA.|Respiratory Consultants, 3366 Oakdale Avenue N, Robbinsdale, MN, 55422, USA.
authors: T
authors: T
authors: Shamp
authors: Biothera Pharmaceutical Inc., 3388 Mike Collins Drive, Eagan, MN, 55121, USA.
authors: M A
authors: MA
authors: Gargano
authors: Biothera Pharmaceutical Inc., 3388 Mike Collins Drive, Eagan, MN, 55121, USA.
authors: R M
authors: RM
authors: Walsh
authors: Biothera Pharmaceutical Inc., 3388 Mike Collins Drive, Eagan, MN, 55121, USA. mpatchen@biothera.com.
authors: M L
authors: ML
authors: Patchen
mesh_terms: D000293:Adolescent; D000328:Adult; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005936:Glucans / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010919:Placebos; D055815:Young Adult; D047071:beta-Glucans / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C000612648:BTH1677; D005936:Glucans; D000069452:Pathogen-Associated Molecular Pattern Molecules; D010919:Placebos; D047071:beta-Glucans; C064197:beta-1,6-glucan
keywords: BTH1677; Beta glucan; Imprime PGG; Pathogen associated molecular pattern; Pharmacokinetics; Safety