Asimadoline for the Treatment of Post-Operative Ileus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of asimadoline in patients who have undergone a laparoscopic segmental colectomy and determine whether it reduces the time to recovery of bowel function compared to placebo.

Detailed Description
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This randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy and tolerability of two dose levels of asimadoline on the duration of post-operative ileus in subjects undergoing laparoscopic or hand-assisted laparoscopic colon resections. Subjects meeting entry criteria were randomized in a 1:1:1 ratio to receive either asimadoline 1.0 mg, asimadoline 3.0 mg or a placebo. One hundred and fourteen subjects were planned, and in the event that a subject was converted from a laparoscopic surgery to an open surgery (laparotomy), that subject would be discontinued from the trial and followed for safety only. The protocol allowed subjects converted to open procedures to be replaced. The first dose was administered approximately 90 minutes pre-operatively, and subsequent dosing was b.i.d. for up to 10 post-operative doses. Subjects were dosed with study drug only while in the hospital. After discharge, they were followed for an additional 28 days. Total study duration for each patient was approximately 5 to 6 weeks.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study Evaluating Asimadoline on the Duration of POI in Subjects Undergoing Laparoscopic/Hand-Assisted Lap Segmental Colonic Resection Secondary to Colon Cancer, Polypectomy or Diverticulitis

Conditions
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Post-Operative Ileus

Intervention / Treatment
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* Drug: Asimadoline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18-80 Must be scheduled to undergo a laparoscopic/hand-assisted laparoscopic segmental colectomy Must sign an ICF Females of childbearing potential must have a negative pregnancy test at screening Exclusion Criteria: Subjects with evidence of a biochemical or structural abnormality of the GI tract or other co-morbid illness that may impact the ability to interpret the safety and efficacy data Pregnant or breastfeeding females Use of investigational drugs in previous 30 days Refusal to discontinue prohibited concomitant medications Chronic use of prescription narcotics over the previous 6 months

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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo was provided in coated tablets identical in appearance to asimadoline tablets. Subjects were given 3 tablets of placebo 90 minutes prior to their operation and then 3 placebo tablets b.i.d. for up to 10 post-operative doses.<br>|
| Active Comparator: Asimadoline 1.0 mg<br>Asimadoline 1.0 mg b.i.d. | Drug: Asimadoline<br>* Asimadoline was provided in coated tablets of 1.0 mg strength. Subjects were given 3 tablets of study drug 90 minutes prior to their operation and then 3 tablets b.i.d. for up to 10 post-operative doses. Subjects randomized to receive 3.0 mg of asimadoline received three 1.0 mg asimadoline tablets at each scheduled dose, while those randomized to receive 1.0 mg of asimadoline received two placebo tablets and one 1.0 mg asimadoline tablet at each scheduled dose.<br>* Other names: EMR 63 320;|
| Active Comparator: Asimadoline 3.0 mg<br>Asimadoline 3.0 mg b.i.d. | Drug: Asimadoline<br>* Asimadoline was provided in coated tablets of 1.0 mg strength. Subjects were given 3 tablets of study drug 90 minutes prior to their operation and then 3 tablets b.i.d. for up to 10 post-operative doses. Subjects randomized to receive 3.0 mg of asimadoline received three 1.0 mg asimadoline tablets at each scheduled dose, while those randomized to receive 1.0 mg of asimadoline received two placebo tablets and one 1.0 mg asimadoline tablet at each scheduled dose.<br>* Other names: EMR 63 320;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Return of Upper and Lower GI Function | The time to first bowel movement or the time to tolerating solid food, whichever occurs later. | Daily for 38 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tolerating Solid Food | Time to tolerating solid food (toleration is defined as the absence of nausea or vomiting) within 4 hours of ingesting a meal | 4 hours of ingesting a meal | 
| Time to First Passage of Flatus |  | Daily for 38 days | 
| Time to First Bowel Movement |  | Daily for 38 days | 
| Time to Writing of Hospital Discharge Order |  | Daily for 38 days | 
| Nausea Score |  | Daily for 38 days | 
| Vomiting Score |  | Daily for 38 days | 
| Pain Score |  | Daily for 38 days | 
| Nasogastric Tube Re-insertion | Proportion of subjects with nasogastric tube re-insertion | Daily for 38 days | 
| Post-operative Analgesic Use |  | Daily for 38 days | 
| Adverse Events | Adverse events grouped by body system | Daily for 38 days | 
| Laboratory Values | Changes in laboratory values. | Daily for 38 days |