NCT04100447

A Study to Evaluate the Safety, Tolerability and Efficacy of LB1148 for Subjects Undergoing Elective Bowel Resection

An Investigator-Sponsored, Open-Label Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of LB1148 for Subjects Undergoing Elective Bowel Resection

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Ronald Hurst, MD, FACS · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Adhesions
• Ileus

Interventions

Type	Name	Description
DRUG	Tranexamic Acid	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.

Timeline

• Start date: 2018-11-05
• Primary completion: 2020-03-20
• Completion: 2020-12-01
• First posted: 2019-09-24
• Last updated: 2020-12-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study