The Safety, Tolerability, and Pharmacokinetics Profile of BT-11, an Oral, Gut-Restricted Lanthionine Synthetase C-Like 2 Agonist Investigational New Drug for Inflammatory Bowel Disease: A Randomized, Double-Blind, Placebo-Controlled Phase I Clinical Trial

Inflamm Bowel Dis. 2020 Mar 4;26(4):643-652. doi: 10.1093/ibd/izz094.


BT-11 is a new oral, gut-restricted, first-in-class investigational drug for Crohn disease (CD) and ulcerative colitis (UC) that targets the lanthionine synthetase C-like 2 (LANCL2) pathway and immunometabolic mechanisms. Oral BT-11 was assessed for safety, tolerability, and pharmacokinetics (PK) in normal healthy volunteers (n = 70) in a randomized, double-blind, placebo-controlled trial. Subjects (n = 70) were randomly assigned to one of five single ascending dose cohorts (up to 100 mg/kg, p.o.) and three multiple ascending dose cohorts [up to 100 mg/kg daily (QD) for seven days, orally]. Safety and tolerability were assessed by adverse event (AE) reporting, vital signs, electrocardiogram, hematology, and clinical chemistry. BT-11 did not increase total or gastrointestinal AE rates, as compared with placebo, and no serious adverse events were observed. Oral BT-11 dosing does not result in any clinically significant findings by biochemistry, coagulation, electrocardiogram, hematology, or urinalysis as compared with placebo. Mean fecal concentrations of BT-11 increased linearly with increasing oral doses, with 2.39 mg/g at 7.7 mg/kg on day 7 of the multiple ascending dose (MAD). Analysis of plasma pharmacokinetics indicates that maximum systemic concentrations are approximately 1/6000th of observed concentrations in feces and the distal gastrointestinal tract. Fecal calprotectin levels were lower in BT-11 treated groups as compared to placebo. BT-11 significantly decreases interferon gamma positive (IFNγ+) and tumor necrosis factor alpha positive (TNFα+) cluster of differentiation 4 positive (CD4+) T cells and increases forkhead box P3 positive (FOXP3+) CD4+ T cells in colonic lamina propria mononuclear cells from patients with CD and patients with UC at concentrations of 0.01 µM when treated ex vivo. BT-11 treatment is well-tolerated with no dose-limiting toxicities up to daily oral doses of 100 mg/kg (16 tablets); whereas the efficacious dose is a single tablet (8 mg/kg). Phase II studies in CD and UC patients are ongoing.

Keywords: BT-11; LANCL2; first-in-human study; gut restricted; inflammatory bowel disease.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Benzimidazoles / pharmacokinetics
  • Benzimidazoles / pharmacology*
  • Double-Blind Method
  • Drugs, Investigational
  • Female
  • Healthy Volunteers
  • Humans
  • Inflammatory Bowel Diseases / pathology*
  • Interferon-gamma / blood
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Male
  • Membrane Proteins / antagonists & inhibitors*
  • Middle Aged
  • Phosphate-Binding Proteins / antagonists & inhibitors*
  • Piperazines / pharmacokinetics
  • Piperazines / pharmacology*
  • Tumor Necrosis Factor-alpha / blood
  • Virginia
  • Young Adult


  • Benzimidazoles
  • Drugs, Investigational
  • LANCL2 protein, human
  • Membrane Proteins
  • N,N-bis(benzimidazolylpicolinoyl)piperazine
  • Phosphate-Binding Proteins
  • Piperazines
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma