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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and efficacy of LB1148 in subjects undergoing planned bowel resection.

Detailed Description
-----------------
This will be a multicenter, randomized, double-blind, placebo-controlled, study to evaluate the safety and efficacy of LB1148 in return to bowel function for subjects undergoing planned bowel resection.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety and Efficacy of LB1148 in Accelerating the Time to Return of Bowel Function in Subjects Undergoing Planned Bowel Resection (INTEGRITY)

Conditions
-----------------
Ileus, Gastro-Intestinal Disorder

Intervention / Treatment
-----------------
* Drug: LB1148
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects will be eligible for participation in the study only if they meet ALL of the following inclusion criteria: Adults age 18 to 80 years, inclusive. Scheduled to undergo a planned (non-emergent) bowel resection via minimally invasive technique or laparotomy. This includes any subject in which a resection of the small intestine, colon, or rectum is performed for any elective indication. Willing to perform and comply with all study procedures including, being hospitalized until achieving GI-2 and responding to telephone follow-up visits as scheduled. Willing and able to provide written informed consent. Exclusion Criteria: Subjects will not be eligible for participation in the study if they meet ANY of the following exclusion criteria: History of total colectomy. Has a preexisting ostomy. History of radiation enteritis. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2. History of seizure disorder. History of myeloproliferative disorders. American Society of Anesthesiologists (ASA) Class IV or V. Inability to take IP orally or consume solid food. Planned treatment with alvimopan (Entereg®) during hospitalization period Chronic opioid usage, defined by the American Pain Society as daily or near-daily use of opioids for at least 90 days. Men and women of child bearing potential (WOCBP) who are unwilling to practice a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with vasectomized partner, vasectomy, hysterectomy, bilateral tubal ligation, licensed hormonal methods (but not combination hormonal methods), intrauterine device, or use of spermicide combined with a barrier method (e.g., condom, diaphragm) for 28 days before Day 1 and through Day 30. Women who will not agree to stop combined hormonal contraceptive and or combined hormonal replacement therapy (including combined hormonal pill, patch or vaginal ring) during the 7 day period prior to Surgery (Study Day 2) through the 7 day period following surgery (Study Days 3 through 9). 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 Receipt of any investigational drug within 28 days or 5 half-lives prior to Day 1. Any other condition that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LB1148<br> | 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> | 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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to return of gastrointestinal function | The later of the times in hours from placement of the last skin staple or suture to the time of toleration of solid food (defined as the time a subject finished a meal that required chewing and experienced no significant nausea/vomiting for 4 hours after the solid meal) and the first bowel movement, up to 14 days post-surgery | From surgical procedure up to 14 days in hospital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first bowel movement | Time in hours from placement of the last skin staple or suture to the time of first bowel movement | From surgical procedure up to 14 days in hospital | 
| Time subject is ready for discharge | Time subject is ready for discharge, defined as the time from the end of surgery to the time the subject is ready for hospital discharge solely based on the recovery of GI function, as determined by the surgeon | From surgical procedure up to 14 days in hospital | 
| Time discharge order written | Time discharge order written, defined as the time from the end of surgery to the time that the hospital discharge order is written | From surgical procedure up to 14 days in hospital | 
| Time of actual discharge | Time of actual discharge, defined as the time from the end of surgery to the time the subject is actually discharged from the hospital | From surgical procedure up to 14 days in hospital | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
enterotomy, post operative ileus, return of bowel function, return of gastrointestinal function, colon surgery, colorectal surgery, intestinal surgery