Amitiza® Plus GoLYTELY® (PEG) Versus Placebo Plus GoLYTELY® for Outpatient Colonoscopy Preparation

Study Overview
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Brief Summary
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The primary objective is to compare the effectiveness and tolerance of the medication named lubiprostone plus a large volume liquid laxative versus placebo which is a look alike medication that has no effect such as a sugar pill plus a large volume liquid laxative as a bowel cleaning preparation for colonoscopy to see the colon better during the colonoscopy to identify abnormal growths such as polyps or colon cancer. Colonoscopy is considered the best way to screen for colon cancer screening because you can visualize the colon directly and remove or biopsy abnormal growths. The limiting step in the procedure is the quality of the colon preparation prior to the procedure. Many patients do not tolerate large volumes of liquid used to prepare the colon. The purpose of the study is to improve the quality of the prep by adding a pill laxative medication before starting the large volume laxative to better see the colon. The other aim of the study is to try to reduce the amount of of liquid laxative the patient has to drink by giving a pill laxative before starting the liquid laxative.

Detailed Description
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The study is a double blind placebo controlled study of lubiprostone in 4 doses vs look alike placebo in 4 doses before bowel preparation for outpatient screening, surveillance and diagnostic colonoscopy. Patients with severe underlying medical conditions were excluded. Patients with inflammatory bowel disease, frequent bowel movements and colonic resection were also excluded. Patients were randomized to one of two groups. The study was double blinded. The first group took lubiprostone 24 micrograms and the second group took look alike placebo in 4 divided doses right before starting the bowel prep with the last dose upon starting polyethylene glycol-electrolyte solution the evening before the colonoscopy. All study patients were educated and instructed to observe for clear stool, which was defined as watery consistency without any solid fecal material or dark liquid stools before stopping the liquid bowel prep. Patients were instructed to return the unused PEG solution on the day of colonoscopy. After completing the preparation but before colonoscopy, patients were also required to fill a questionnaire to assess the tolerability of tablets and solution. This was measured on a 1-5 rating Likert scale (1) Easy, 2) Tolerable, 3) Slightly Difficult, 4) Extremely Difficult, and 5)Unable to Finish and was based on the patient's ability to swallow the liquid and each of 4 tablets. In addition, the pres- ence of symptoms of nausea, vomiting, abdominal pain, chest pain, dizziness, and bloating was evaluated. The primary endpoints was the endoscopist's evaluation of the preparation quality. All colonoscopies were performed by 3 endoscopists (with 85% of the procedures performed by principal investigator of the study, A.L.S.). Endo- scopists evaluated the quality of the colonoscopy prep- aration based on the previously validated Ottawa bowel preparation scale.5 This scale rates 3 sections of colon, rectosigmoid, mid, and right colon, on a 5-point scale (0-4) and a global 3-point rating (0-2) for overall colonic fluid. The total score ranges from 0-14; score of 0 being perfect and score of 14 indicating solid stool in each colon segment and lot of fluid.The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group.

Official Title
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Lubiprostone Plus Polyethylene Glycol-electrolyte Solutionvs. Placebo Plus Polyethylene Glycol-electrolyte Solution for Outpatient Colonoscopy Preparation: A Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Colonoscopy

Intervention / Treatment
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* Drug: lubiprostone (Amitiza)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 18 years old Subject is in good health Subject is undergoing a screening, surveillance or diagnostic colonoscopy Subject has a spontaneous bowel movement at least every 48 hours Exclusion Criteria: Subject has renal insufficiency demonstrated by serum creatinine > 1.4mg/dL Subject has Type 1 diabetes Subject has past or present diagnosis of Congestive Heart Failure Subject has past or present diagnosis of inflammatory bowel disease Subject had previous colon resection Subject has a preexisting electrolyte abnormality Subject has more than 3 spontaneous bowel movements daily

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Active Comparator: Ingested 4 tablets of lubiprostone in divided doses + 1 gallon of polyethylene glycol<br>First dose of lubiprostone 24 micrograms or placebo was administered 2 nights before colonoscopy and subsequent doses at breakfast, lunch, and dinner on the day before the procedure. Patients were on a clear liquid diet on the day before the procedure and were instructed to initiate drinking PEG (immediately after the last dose of lubiprostone) at 6 PM the evening before the colonoscopy and continued drinking the solution until at least 2 bowel movements were clear yellow or green. All study patients were educated and instructed to observe for clear stool, which was defined as watery consistency without any solid fecal material or dark liquid stools. Patients were instructed to return the unused PEG solution on the day of colonoscopy. After completing the preparation but before colonoscopy, patients were also required to fill a questionnaire to assess the tolerability of tablets and solution. | Drug: lubiprostone (Amitiza)<br>* 24 mcg administered 4 times over the two days before the colonoscopy. 96 mcg total<br>* Other names: Amitiza;|
| Placebo Comparator: Ingested 4 tablets of placebo in divided doses + 1 gallon of polyethylene glycol<br>First dose of look alike placebo was administered 2 nights before colonoscopy and subsequent doses at breakfast, lunch, and dinner on the day before the procedure. Patients were on a clear liquid diet on the day before the procedure and were instructed to initiate drinking PEG (immediately after the last dose of lubiprostone) at 6 PM the evening before the colonoscopy and continued drinking the solution until at least 2 bowel movements were clear yellow or green. All study patients were educated and instructed to observe for clear stool, which was defined as watery consistency without any solid fecal material or dark liquid stools. Patients were instructed to return the unused PEG solution on the day of colonoscopy. After completing the preparation but before colonoscopy, patients were also required to fill a questionnaire to assess the tolerability of tablets and solution. | Drug: Placebo<br>* Amitiza Placebo<br>* Other names: Look alike placebo Amitiza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endoscopist Evaluation of Colon Cleanliness in the Lubiprostone Group vs the Placebo Group | Endoscopists evaluated the quality of the colonoscopy preparation based on Ottawa bowel preparation scale. . The total score ranges from 0-14; score of 0 being perfect and score of 14 indicating solid stool in each colon segment and lot of fluid. Before using the scale for this trial, the endoscopists participated in a calibration exercise that involved 20 patients to ensure that they concurred on their interpretation of the scale. | within 12 hours of completing bowel prep | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | After completing the colonoscopy prep patients were asked to assess tolerability of the prep using a 5 point Likert scale with 1 being easy and 5 being unable to complete the prep | done at the time of colonoscopy | 
| Change in Volume of PEG From Beginning of Bowel Prep to That at Completion of the Colonoscopy Preparation in the Two Groups | Patients in the lubiprostone group and the placebo returned unused PEG after completing the prep for the colonoscopy. This was measured in liters and recorded. | amount of PEG at start of the study and that measured when the patient presented for their procedure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Routine screening colonoscopy, Colonoscopy Preparation, Amitiza, GoLYTELY, Pegylated Electrolytes, Preparation Solution, Colonoscopy Solution