A Study to Evaluate LB1148 for Return of Gastrointestinal Function and Adhesions in Subjects Undergoing Bowel Resection

Study Overview
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Brief Summary
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The purpose of this study is to establish preliminary evidence of the efficacy, safety, and tolerability of LB1148 for the treatment of post-operative ileus and intra-abdominal adhesions in subjects undergoing elective bowel resection.

Detailed Description
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This will be a multicenter, randomized, double-blind, parallel, placebo-controlled, proof-of-concept, adaptive design, Phase 2 study to evaluate LB1148 for return of gastrointestinal function and reduction of post-operative ileus and intra-abdominal adhesions in subjects undergoing elective bowel resection surgery with or without a planned stoma.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Proof of Concept Study to Evaluate LB1148 for Return of Gastrointestinal Function, Post-Operative Ileus and Intra-Abdominal Adhesions in Subjects Undergoing Elective Bowel Resection

Conditions
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Ileus, Post-Operative Adhesions

Intervention / Treatment
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* Drug: LB1148
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible for participation in the study only if they meet ALL of the following inclusion criteria: Scheduled to undergo an elective (non-emergent) bowel resection with a planned stoma via laparotomy or minimally invasive technique. This includes any subject in which a resection of the small intestine, colon, or rectum is performed for any elected indication. Planned stoma takedown or other planned abdominal surgery within 8 months of the initial surgery. Willing to perform and comply with all study procedures including attending clinic visit as scheduled and completion of a second surgery for stoma takedown or other abdominal surgery and to determine the presence of intra-abdominal adhesions. Has been informed of the nature of the study (either the subject or their legal representative), agrees to its provisions, and has provided written informed consent. Exclusion Criteria: Subjects will not be eligible for participation in the study if they meet ANY of the following exclusion criteria: <18 or >80 years of age. Requires emergency bowel surgery. Has had 1 or more abdominal surgeries, excluding the current, for inflammatory bowel disease, including, but not limited to, inflammatory bowel disease (IBD), Crohn's Disease, or ulcerative colitis. Note: This does not apply to previous surgery such as hernia repair unrelated to IBD. American Society of Anesthesiologists (ASA) Class 4 or 5. Known inability to take the study drug orally (i.e. complete small bowel obstruction). Has contraindications or potential risk factors to taking TXA. These include subjects with: Known sensitivity to TXA; Recent craniotomy (past 30 days); Active cerebrovascular bleed; Active thromboembolic disease (such as deep vein thrombosis, pulmonary embolism, cerebral thrombosis, ischemic stroke, or acute coronary syndrome); Acute promyelocytic leukemia taking all-trans retinoic acid for remission induction, or Continuing use of a combined hormonal contraceptive and or combined hormonal replacement therapy (including combined hormonal pill, patch, or vaginal ring). Has peritoneal carcinomatosis History of or current seizure disorder. Patients with myeloproliferative disorders. Any other condition that, in the opinion of the Investigator, would preclude the subject from being an appropriate candidate for the study, including severe renal or hepatic impairment. Planned treatment with alvimopan (Entereg®) during study participation period. Planned use of 4% icodextrin (Adept®) or SEPRAFILM during the first surgery. Received any other investigational therapy within 4 weeks prior to Randomization Female subjects of childbearing potential with a positive urine or serum pregnancy test or who are not taking (or not willing to take) acceptable birth control measures (abstinence, intrauterine devices, contraceptive implants or barrier methods) through Day 30. Additionally, those women who are lactating and insist on breast feeding within 5 days of the last dose of study drug. Known history of radiation enteritis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LB1148<br>Active | Drug: LB1148<br>* A total of 700 mL of drug product will be administered orally as a split dose before surgery.<br>* Other names: Active;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* A total of 700 mL of placebo will be administered orally as a split dose before surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in extent and severity of intra-abdominal adhesions among subjects treated with LB1148 or placebo | Extent and severity of intra-abdominal adhesions will be determined by the surgeon using the Intra-Abdominal Adhesion Extent and Severity Assessment Worksheet | up to 8 months from the index surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from surgical closure to resolution or appearance, as appropriate, of 1 or more of the components common to GI dysfunction following elective bowel resection with or without a planned stoma | Compare time from surgical closure to resolution or appearance, as appropriate, of 1 or more of the components common to gastrointestinal (GI) dysfunction following elective bowel resection with a planned stoma. | From surgical closure up to 14 days in hospital | 
| Time to return of gastrointestinal function as defined by achieving GI2 | GI2 is a composite endpoint defined as the time from the end of surgery to the time of recovery of the upper GI tract (toleration of solid food) and the time to recovery of the lower GI tract (first bowel movement). | From surgical closure up to 14 days in hospital | 
| Time to Achieve GI-3 | GI3 is defined as the toleration of solid food and either first flatus or bowel movement | From surgical closure up to 14 days in hospital | 
| Time to resolution of post-operative ileus | Compare number of hours to resolution of POI. | From surgical closure up to 14 days in hospital | 
| Hospital length of stay | Compare hospital length of stay (LOS, recorded in hours) through Discharge or Day 14 (whichever comes first). | From surgical closure up to 14 days in hospital | 
| Incidence of intra-abdominal adhesions | Compare the incidence of intra-abdominal adhesions following the second surgery among subjects treated with LB1148 or placebo. | up to 8 months from the index surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-operative Ileus, Post-Operative Abdominal Adhesions, Return of Gastrointestinal Function, Anastomosis, Enterotomy, Enterostomy, Colorectal Surgery, Intestines Surgery