PMID- 26865390
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20181113
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 34
IP  - 2
DP  - 2016 Apr
TI  - 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.
PG  - 202-15
LID - 10.1007/s10637-016-0325-z [doi]
AB  - 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 (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.
FAU - Halstenson, C E
AU  - Halstenson CE
AD  - Prism Research, 1000 Westgate Drive, St. Paul, MN, 55114, USA.
FAU - Shamp, T
AU  - Shamp T
AD  - Prism Research, 1000 Westgate Drive, St. Paul, MN, 55114, USA.
AD  - Respiratory Consultants, 3366 Oakdale Avenue N, Robbinsdale, MN, 55422, USA.
FAU - Gargano, M A
AU  - Gargano MA
AD  - Biothera Pharmaceutical Inc., 3388 Mike Collins Drive, Eagan, MN, 55121, USA.
FAU - Walsh, R M
AU  - Walsh RM
AD  - Biothera Pharmaceutical Inc., 3388 Mike Collins Drive, Eagan, MN, 55121, USA.
FAU - Patchen, M L
AU  - Patchen ML
AD  - Biothera Pharmaceutical Inc., 3388 Mike Collins Drive, Eagan, MN, 55121, USA. 
      mpatchen@biothera.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160211
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (BTH1677)
RN  - 0 (Glucans)
RN  - 0 (Pathogen-Associated Molecular Pattern Molecules)
RN  - 0 (Placebos)
RN  - 0 (beta-Glucans)
RN  - 37361-00-5 (beta-1,6-glucan)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Demography
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Glucans/*administration & dosage/adverse effects/pharmacokinetics/*pharmacology
MH  - *Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Pathogen-Associated Molecular Pattern Molecules/*administration & 
      dosage/pharmacokinetics/*pharmacology
MH  - Placebos
MH  - Young Adult
MH  - beta-Glucans/*administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
PMC - PMC4786610
OTO - NOTNLM
OT  - BTH1677
OT  - Beta glucan
OT  - Imprime PGG
OT  - Pathogen associated molecular pattern
OT  - Pharmacokinetics
OT  - Safety
EDAT- 2016/02/13 06:00
MHDA- 2016/12/15 06:00
PMCR- 2016/02/11
CRDT- 2016/02/12 06:00
PHST- 2015/12/02 00:00 [received]
PHST- 2016/01/10 00:00 [accepted]
PHST- 2016/02/12 06:00 [entrez]
PHST- 2016/02/13 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2016/02/11 00:00 [pmc-release]
AID - 10.1007/s10637-016-0325-z [pii]
AID - 325 [pii]
AID - 10.1007/s10637-016-0325-z [doi]
PST - ppublish
SO  - Invest New Drugs. 2016 Apr;34(2):202-15. doi: 10.1007/s10637-016-0325-z. Epub 
      2016 Feb 11.