Post-Operative Ileus
Conditions
Brief summary
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
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.
Interventions
DRUGAsimadoline
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.
DRUGPlacebo
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.
Sponsors
RTI Health Solutions
Tioga Pharmaceuticals
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Return of Upper and Lower GI Function | Daily for 38 days | The time to first bowel movement or the time to tolerating solid food, whichever occurs later. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Tolerating Solid Food | 4 hours of ingesting a meal | Time to tolerating solid food (toleration is defined as the absence of nausea or vomiting) within 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 | Daily for 38 days | Proportion of subjects with nasogastric tube re-insertion |
| Post-operative Analgesic Use | Daily for 38 days | — |
| Adverse Events | Daily for 38 days | Adverse events grouped by body system |
| Laboratory Values | Daily for 38 days | Changes in laboratory values. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asimadoline 1.0 mg Asimadoline 1.0 mg b.i.d. | 14 |
| Asimadoline 3.0 mg Asimadoline 3.0 mg b.i.d. | 11 |
| Placebo Matching Placebo | 10 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Converted to an open laparotomy | 3 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Asimadoline 3.0 mg | Placebo | Asimadoline 1.0 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 4 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 10 Participants | 22 Participants |
| Age Continuous | 60 years STANDARD_DEVIATION 12.9 | 57 years STANDARD_DEVIATION 15.3 | 58 years STANDARD_DEVIATION 9.7 | 58 years STANDARD_DEVIATION 12.2 |
| Region of Enrollment United States | 11 participants | 10 participants | 14 participants | 35 participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 14 | 11 / 11 | 10 / 10 |
| serious Total, serious adverse events | 0 / 14 | 1 / 11 | 1 / 10 |
Outcome results
Primary
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.
Time frame: Daily for 38 days
Population: As the study was terminated early due to poor enrollment (31 of a planned 114 subjects were randomized and evaluable), no formal efficacy analyses were conducted.
Secondary
Adverse Events
Adverse events grouped by body system
Time frame: Daily for 38 days
Secondary
Laboratory Values
Changes in laboratory values.
Time frame: Daily for 38 days
Secondary
Nasogastric Tube Re-insertion
Proportion of subjects with nasogastric tube re-insertion
Time frame: Daily for 38 days
Secondary
Nausea Score
Time frame: Daily for 38 days
Secondary
Pain Score
Time frame: Daily for 38 days
Secondary
Post-operative Analgesic Use
Time frame: Daily for 38 days
Secondary
Time to First Bowel Movement
Time frame: Daily for 38 days
Secondary
Time to First Passage of Flatus
Time frame: Daily for 38 days
Secondary
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
Time frame: 4 hours of ingesting a meal
Secondary
Time to Writing of Hospital Discharge Order
Time frame: Daily for 38 days
Secondary
Vomiting Score
Time frame: Daily for 38 days