A Study to Evaluate the Safety, Tolerability and Efficacy of LB1148 for Subjects Undergoing Elective Bowel Resection
Condition: Adhesions; Ileus
MeSH terms: Tissue Adhesions
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess the safety, tolerability, and preliminary efficacy of
      LB1148 in subjects undergoing elective bowel resection. During abdominal surgery, surgeons
      handle, manipulate, and often make incisions in the bowel. These actions can create bruising,
      lesions, and microscopic damage to the bowel, which may allow digestive enzymes to cross the
      intestinal mucosal barrier potentially resulting in injury both locally and remotely. Leaking
      digestive enzymes may delay return of normal gastrointestinal (GI) function, lead to a lack
      of motility in the intestine (ileus), and promote the formation of intestinal scar tissue
      (adhesions).
    

Detailed description: 
      The intestinal mucosal barrier plays a key role in both acute critical care medical
      conditions as well as burdensome chronic diseases. Healthy maintenance of the intestinal
      mucosal barrier requires oxygenation and blood flow and avoidance of mechanical or physical
      injury. Potent digestive enzymes are maintained within the intestine as long as normal blood
      flow continues and no damage or disturbances to the wall occur.

      Breakdown of the intestinal mucosal barrier can be produced by wide variety of events. These
      include prolonged low blood pressure (e.g. during shock), disruption of blood flow (e.g.
      during ischemia), and physical and mechanical perturbations (e.g. during trauma or abdominal
      surgery).

      One of the key advances toward the use of LB1148 to reduce postoperative complications was
      the learning that with more subtle perturbations of the mucosal barriers, such as during
      abdominal surgery, intraluminal pancreatic digestive enzymes played a role in GI dysfunction.
      Perioperative oral administration of LB1148 in preclinical models was sufficient to reduce
      the delayed return of GI function. Furthermore, the reduction in pancreatic digestive
      enzyme-induced tissue damage resulted in a profound reduction in postoperative adhesion
      formation. Together, these preclinical studies provide evidence that blocking pancreatic
      digestive enzymes with LB1148 in the intestine reduces local tissue damage, preserves GI
      function, and reduces adhesion formation.
    

Intervention name(s): Tranexamic Acid
Intervention type(s): Drug
Intervention description(s): A total of 700 mL of study drug should be completely consumed orally 2-12 hours prior to surgery as a split dose; 350 mL 6-12 hours prior to surgery and the remaining 350 mL 2-6 hours prior to surgery.
Other intervention name(s): LB1148
Intervention MeSH terms: Tranexamic Acid
Intervention model: Single Group Assignment
Intervention model description: This is an investigator-initiated, open label, Phase 1 study to evaluate LB1148 for safety, tolerability, and preliminary efficacy in subjects undergoing elective bowel resection. All subjects will receive LB1148 prior to surgery.
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: post-operative; abdominal