Ileus, Post-Operative Adhesions
Conditions
Keywords
Post-operative Ileus, Post-Operative Abdominal Adhesions, Return of Gastrointestinal Function, Anastomosis, Enterotomy, Enterostomy, Colorectal Surgery, Intestines Surgery
Brief summary
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
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.
Interventions
DRUGPlacebo
A total of 700 mL of placebo will be administered orally as a split dose before surgery.
DRUGLB1148
A total of 700 mL of drug product will be administered orally as a split dose before surgery.
Sponsors
Palisade Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Subjects will be eligible for participation in the study only if they meet ALL of the following inclusion criteria: 1. 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. 2. Planned stoma takedown or other planned abdominal surgery within 8 months of the initial surgery. 3. 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. 4. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Extent and Severity of Intra-abdominal Adhesions Among Subjects Treated With LB1148 or Placebo | up to 8 months from the index surgery | Extent and severity of intra-abd. adhesions will be determined by the surgeon using the Intra-Abdominal Adhesion Extent and Severity Assessment Worksheet with a min. value of zero (0) (better) and a max. value of one hundred and eight (108) (worse). And which records four (4) Sub scores for nine (9) abd. regions which are all summed to make the Total Extent and severity score. Sub scores include: 1) Abd. Wall to Bowel Extent Score (0-3); 2) Abd. Wall to Bowl Severity Score (0-3); Bowel to Bowel (or Viscera) Extent Score (0-3); Bowel to Bowel (or Viscera) Severity Score (0-3); The nine (9) Abd. Regions include: Right upper; Epigastrium; Left upper; Left flank; Left lower; Pelvis; Right lower; Right flank; and Central. Each Sub score is scored with a min. value of zero (0) (better) and a max. value of three (3) (worse); 0=no adhesion; 1=min. (\<1/3 of the site is covered); 2=mod. (1/3 to 2/3 of the site is covered); 3=extensive (\>2/3 of the site is covered). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LB1148 Active
LB1148: A total of 700 mL of drug product was administered orally as a split dose before surgery. | 57 |
| Placebo Placebo
Placebo: A total of 700 mL of placebo was administered orally as a split dose before surgery. | 55 |
| Total | 112 |
Baseline characteristics
| Characteristic | Placebo | Total | LB1148 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 40 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 72 Participants | 36 Participants |
| Age, Continuous | 55.9 years STANDARD_DEVIATION 13.94 | 57.6 years STANDARD_DEVIATION 12.85 | 59.4 years STANDARD_DEVIATION 11.56 |
| Race/Ethnicity, Customized American Indian | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black | 3 participants | 6 participants | 3 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 2 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized White/Caucasian | 49 participants | 101 participants | 52 participants |
| Region of Enrollment United States | 55 participants | 112 participants | 57 participants |
| Sex: Female, Male Female | 24 Participants | 48 Participants | 24 Participants |
| Sex: Female, Male Male | 31 Participants | 64 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 57 | 0 / 55 |
| other Total, other adverse events | 38 / 57 | 40 / 55 |
| serious Total, serious adverse events | 16 / 57 | 14 / 55 |
Outcome results
Primary
Change From Baseline in Extent and Severity of Intra-abdominal Adhesions Among Subjects Treated With LB1148 or Placebo
Extent and severity of intra-abd. adhesions will be determined by the surgeon using the Intra-Abdominal Adhesion Extent and Severity Assessment Worksheet with a min. value of zero (0) (better) and a max. value of one hundred and eight (108) (worse). And which records four (4) Sub scores for nine (9) abd. regions which are all summed to make the Total Extent and severity score. Sub scores include: 1) Abd. Wall to Bowel Extent Score (0-3); 2) Abd. Wall to Bowl Severity Score (0-3); Bowel to Bowel (or Viscera) Extent Score (0-3); Bowel to Bowel (or Viscera) Severity Score (0-3); The nine (9) Abd. Regions include: Right upper; Epigastrium; Left upper; Left flank; Left lower; Pelvis; Right lower; Right flank; and Central. Each Sub score is scored with a min. value of zero (0) (better) and a max. value of three (3) (worse); 0=no adhesion; 1=min. (\<1/3 of the site is covered); 2=mod. (1/3 to 2/3 of the site is covered); 3=extensive (\>2/3 of the site is covered).
Time frame: up to 8 months from the index surgery
Population: The protocol from July 11 '16 underwent 6 amendments. The Safety Population included all randomized subjects (n=112). The modified Intention to Treat (mITT) population comprised subjects meeting criteria and receiving full dose with no key deviations (n=33). Those completing per protocol (PP) were (n=22). The smaller evaluable populations for Outcome Measures vs. Safety Population are due to Second Surgery completion requirements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LB1148 | Change From Baseline in Extent and Severity of Intra-abdominal Adhesions Among Subjects Treated With LB1148 or Placebo | Minimally Invasive Approach | 20.3 total extent and severity scores | Standard Deviation 23.77 |
| LB1148 | Change From Baseline in Extent and Severity of Intra-abdominal Adhesions Among Subjects Treated With LB1148 or Placebo | Laparotomy Approach | 4.0 total extent and severity scores | — |
| Placebo | Change From Baseline in Extent and Severity of Intra-abdominal Adhesions Among Subjects Treated With LB1148 or Placebo | Minimally Invasive Approach | 4.3 total extent and severity scores | Standard Deviation 5.87 |
| Placebo | Change From Baseline in Extent and Severity of Intra-abdominal Adhesions Among Subjects Treated With LB1148 or Placebo | Laparotomy Approach | 8.5 total extent and severity scores | Standard Deviation 9.19 |