Asimadoline for the Treatment of Post-Operative Ileus

• Sponsor: Tioga Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00443040
• Collaborator: RTI Health Solutions (Other)
• Enrollment: 35
• Locations: 4
• Arms: 3
• Duration (Months): 13
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Post-Operative Ileus	Drug: Asimadoline; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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.
Active Comparator: Asimadoline 1.0 mg Asimadoline 1.0 mg b.i.d.	Drug: Asimadoline; 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.; Other Names: EMD 61 753 EMR 63 320
Active Comparator: Asimadoline 3.0 mg Asimadoline 3.0 mg b.i.d.	Drug: Asimadoline; 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.; Other Names: EMD 61 753 EMR 63 320

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. Time to First Passage of Flatus [Daily for 38 days]

3. Time to First Bowel Movement [Daily for 38 days]

4. Time to Writing of Hospital Discharge Order [Daily for 38 days]

5. Nausea Score [Daily for 38 days]

6. Vomiting Score [Daily for 38 days]

7. Pain Score [Daily for 38 days]

8. Nasogastric Tube Re-insertion [Daily for 38 days]

   Proportion of subjects with nasogastric tube re-insertion

9. Post-operative Analgesic Use [Daily for 38 days]

10. Adverse Events [Daily for 38 days]

    Adverse events grouped by body system

11. Laboratory Values [Daily for 38 days]

    Changes in laboratory values.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lahey Clinic	Burlington	Massachusetts	United States	01805
2	Washington University	St. Louis	Missouri	United States	63110
3	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106-5047
4	Marks Colorectal Surgical Associates	Wynnewood	Pennsylvania	United States	19096

Sponsors and Collaborators

• Tioga Pharmaceuticals
• RTI Health Solutions

Investigators

• Study Chair: Allen Mangel, MD, PhD, CMO

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tioga Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00443040
• Other Study ID Numbers: ASMP2004
• First Posted: Mar 5, 2007
• Last Update Posted: Jan 6, 2012
• Last Verified: Nov 1, 2011

• Additional relevant MeSH terms: Ileus

Study Results

Participant Flow

Arm/Group Title	Asimadoline 1.0 mg	Asimadoline 3.0 mg	Placebo
Arm/Group Description	Asimadoline 1.0 mg b.i.d.	Asimadoline 3.0 mg b.i.d.	Matching Placebo
Period Title: Overall Study
STARTED	14	11	10
COMPLETED	10	11	9
NOT COMPLETED	4	0	1

Baseline Characteristics

Arm/Group Title	Asimadoline 1.0 mg	Asimadoline 3.0 mg	Placebo	Total
Arm/Group Description	Asimadoline 1.0 mg b.i.d.	Asimadoline 3.0 mg b.i.d.	Matching Placebo	Total of all reporting groups
Overall Participants	14	11	10	35
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	10 71.4%	6 54.5%	6 60%	22 62.9%
>=65 years	4 28.6%	5 45.5%	4 40%	13 37.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (9.7)	60 (12.9)	57 (15.3)	58 (12.2)
Sex: Female, Male (Count of Participants)
Female	5 35.7%	7 63.6%	3 30%	15 42.9%
Male	9 64.3%	4 36.4%	7 70%	20 57.1%
Region of Enrollment (participants) [Number]
United States	14 100%	11 100%	10 100%	35 100%

Outcome Measures

1. Secondary Outcome

Title	Time to Tolerating Solid Food
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

2. Secondary Outcome

Title	Time to First Passage of Flatus
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time to First Bowel Movement
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Time to Writing of Hospital Discharge Order
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Nausea Score
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Vomiting Score
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Pain Score
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Asimadoline 1.0 mg	Asimadoline 3.0 mg	Placebo
Arm/Group Description	Asimadoline 1.0 mg b.i.d.	Asimadoline 3.0 mg b.i.d.	Matching Placebo
Measure Participants	0	0	0

9. Secondary Outcome

Title	Nasogastric Tube Re-insertion
Description	Proportion of subjects with nasogastric tube re-insertion
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Post-operative Analgesic Use
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Adverse Events
Description	Adverse events grouped by body system
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Laboratory Values
Description	Changes in laboratory values.
Time Frame	Daily for 38 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Asimadoline 1.0 mg		Asimadoline 3.0 mg		Placebo
Arm/Group Description	Asimadoline 1.0 mg b.i.d.		Asimadoline 3.0 mg b.i.d.		Matching Placebo
All Cause Mortality
	Asimadoline 1.0 mg		Asimadoline 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Asimadoline 1.0 mg		Asimadoline 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		1/11 (9.1%)		1/10 (10%)
Gastrointestinal disorders
bleeding gastric ulcer	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
omental necrosis	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Asimadoline 1.0 mg		Asimadoline 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100%)		11/11 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	0/14 (0%)	0	2/11 (18.2%)	2	0/10 (0%)	0
Cardiac disorders
Atrial fibrillation	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Sinus tachycardia	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Supraventricular extrasystoles	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Supraventricular tachycardia	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Tachycardia	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Ventricular extrasystoles	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Ear and labyrinth disorders
Ear Pain	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Gastrointestinal disorders
Nausea	5/14 (35.7%)	5	7/11 (63.6%)	7	4/10 (40%)	4
Abdominal Pain	6/14 (42.9%)	6	5/11 (45.5%)	5	3/10 (30%)	3
Vomiting	1/14 (7.1%)	1	4/11 (36.4%)	4	0/10 (0%)	0
Abdominal Distension	4/14 (28.6%)	4	1/11 (9.1%)	1	0/10 (0%)	0
Diarrhea	2/14 (14.3%)	2	1/11 (9.1%)	1	0/10 (0%)	0
Abdominal discomfort	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Constipation	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Dyspepsia	0/14 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	1
Flatulence	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Melaena	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Painful defaecation	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Intestinal functional disorder	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
General disorders
Asthenia	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Pain	1/14 (7.1%)	1	1/11 (9.1%)	1	0/10 (0%)	0
Pyrexia	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Suprapubic pain	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Infections and infestations
Wound Infection	1/14 (7.1%)	1	2/11 (18.2%)	2	1/10 (10%)	1
Gastroenteritis	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Herpes zoster	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Upper respiratory tract infection	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Injury, poisoning and procedural complications
Procedural Pain	4/14 (28.6%)	4	5/11 (45.5%)	5	6/10 (60%)	6
Incision Site Pain	3/14 (21.4%)	3	0/11 (0%)	0	1/10 (10%)	1
Wound complication	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Incision site haematoma	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Incision site erythema	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Procedural nausea	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Investigations
Potassium Decreased	1/14 (7.1%)	1	1/11 (9.1%)	1	1/10 (10%)	1
Blood sodium decreased	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Haematocrit decreased	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Haemoglobin decreased	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Lymphocyte count decreased	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Neutrophil count increased	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Platelet count decreased	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Red blood cell count decreased	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Weight decreased	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Blood phosphorus decreased	1/14 (7.1%)	1	0/11 (0%)	0	1/10 (10%)	1
Urine output decreased	1/14 (7.1%)	1	1/11 (9.1%)	1	0/10 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Hyponatraemia	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Decreased appetite	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Flank pain	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Groin pain	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Musculoskeletal pain	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Nervous system disorders
Headache	2/14 (14.3%)	2	2/11 (18.2%)	2	1/10 (10%)	1
Burning sensation	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Dizziness	0/14 (0%)	0	2/11 (18.2%)	2	0/10 (0%)	0
Neuralgia	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Paraesthesia	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Syncope	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Psychiatric disorders
Confusional State	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Renal and urinary disorders
Calculus ureteric	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Haematuria	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Pneumaturia	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Urinary retention	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/14 (7.1%)	1	0/11 (0%)	0	0/10 (0%)	0
Pharyngolaryngeal pain	0/14 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/14 (7.1%)	1	0/11 (0%)	0	1/10 (10%)	1
Vascular disorders
Hypertension	0/14 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Hypotension	1/14 (7.1%)	1	1/11 (9.1%)	1	0/10 (0%)	0

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed; no efficacy analysis was completed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator understands and agrees that the first publication of the results of the Research Study, if any, shall be a multicenter publication of the results from all sites. Institution shall not publish, present, or use any results of the Research Study for any purpose until such Research Study has been completed in its entirety at all sites and until such multi-center study publication has been published or for a period of one year following such completion, whichever occurs first.