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
|
---|---|
Published in |
Investigational New Drugs, February 2016
|
DOI | 10.1007/s10637-016-0325-z |
Pubmed ID | |
Authors |
C. E. Halstenson, T. Shamp, M. A. Gargano, R. M. Walsh, M. L. Patchen |
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. Subjects and Methods In the Phase 1a single-dosing study, subjects were randomized (3:1 per cohort) to a single intravenous (iv) 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 iv 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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 46 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 7 | 15% |
Student > Bachelor | 7 | 15% |
Researcher | 6 | 13% |
Other | 5 | 11% |
Student > Ph. D. Student | 4 | 9% |
Other | 8 | 17% |
Unknown | 9 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 12 | 26% |
Nursing and Health Professions | 4 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 7% |
Biochemistry, Genetics and Molecular Biology | 3 | 7% |
Agricultural and Biological Sciences | 3 | 7% |
Other | 7 | 15% |
Unknown | 14 | 30% |