A Phase III Study With FE 999169 Versus Niflec for Colon Cleansing

Study Overview
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Brief Summary
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To demonstrate non inferiority of a) FE 999169 Split Dosing Schedule (one dose on the day before and the second dose on the day of colonoscopy) and b) FE 999169 Day Before Dosing Schedule (two doses on the day before colonoscopy) to  Niflec On the Day Dosing Schedule in subjects requiring colonoscopy.

Detailed Description
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This was a phase III, randomized, assessor-blinded, parallel-arm, multicenter, study in Japanese patients. Patients, who signed an informed consent and fulfilled all screening criteria, were randomized in a 1:1:1 ratio to one of the following 3 treatment groups: FE 999169 Split Dosing Schedule, FE 999169 Day Before Dosing Schedule and  Niflec On the Day Dosing Schedule in subjects requiring colonoscopy.

Official Title
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A Phase III, Randomized, Assessor-Blinded, Parallel-Group, Multi-Centre, Clinical Study With FE 999169 for Oral Administration Versus Niflec® for Colon Cleansing: J-CLEAR

Conditions
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Colon Cleansing in Preparation for Colonoscopy

Intervention / Treatment
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* Drug: FE 999169
* Drug: Niflec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese patients, age 20 to 80 years inclusive, requiring colonoscopy Female patients should be post-menopausal (women ≥45 years with no menstrual period for at least 12 months without an alternative medical cause), or be surgically sterile, or be using medically approved contraception, throughout the trial period. Fertile female patients must have a confirmed negative pregnancy test at screening and randomization Patients must have had more than or equal to 3 spontaneous bowel movements per week prior to the colonoscopy Written informed consent obtained prior to any study-related procedure Exclusion Criteria: Acute surgical abdominal conditions, such as acute intestinal obstruction or intestinal perforation, diverticulitis, appendicitis. If intestinal obstruction and perforation are suspected, perform appropriate diagnostic studies to rule out these conditions Active (acute/exacerbation of/severe/uncontrolled) Inflammatory Bowel Disease (IBD) Any prior colorectal surgery, excluding appendectomy, haemorrhoid surgery or prior endoscopic procedures Colon disease (history of colonic cancer, toxic megacolon, idiopathic pseudo-obstruction, hypomotility syndrome) Gastrointestinal disorder (active ulcer, outlet obstruction, retention, gastroparesis, ileus) Ascites. Upper gastrointestinal surgery (gastric resection, gastric banding, gastric by-pass) Uncontrolled angina and/or Myocardial Infarction (MI) within last 3 months, Congestive Heart Failure (CHF), or uncontrolled hypertension Renal insufficiency (any of the serum creatinine, or serum potassium value exceeding the upper limits of the normal range at screening) or a history of this event Participation in any other clinical trial during the past 3 months Any clinically significant laboratory value at screening, including pre-existing electrolyte abnormality, based on clinical history that the investigators feel may affect the study evaluation Hypersensitivity to active ingredients Subject who cannot suspend the prohibited medications Subjects not appropriate to participate in the study as deemed by the investigator

Ages Eligible for Study
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Minimum Age: 20 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm [1]: FE 999169<br>One sachet on the day before colonoscopy, and another sachet on the day of colonoscopy | Drug: FE 999169<br>* FE 999169 is a white crystalline powder for oral solution. Each sachet (16.1 g) contains sodium picosulfate hydrate 10 mg, magnesium oxide 3.5 g and anhydrous citric acid 12 g as well as orange flavour, potassium bicarbonate and sodium saccharin as excipients. FE 999916 is dissolved by mixing the contents of the sachet with approximately 150mL of cold water in a cup before administration.<br>|
| Experimental: Treatment arm [2]: FE 999169<br>Two sachets on the day before colonoscopy | Drug: FE 999169<br>* FE 999169 is a white crystalline powder for oral solution. Each sachet (16.1 g) contains sodium picosulfate hydrate 10 mg, magnesium oxide 3.5 g and anhydrous citric acid 12 g as well as orange flavour, potassium bicarbonate and sodium saccharin as excipients. FE 999916 is dissolved by mixing the contents of the sachet with approximately 150mL of cold water in a cup before administration.<br>|
| Active Comparator: Treatment arm [3]: Niflec<br>One to two pack(s) on the day of colonoscopy | Drug: Niflec<br>* Niflec is a white-yellowish powder for oral solution. Each plastic sachet (137.155 g) contains sodium chloride 2.93 g, potassium chloride 1.485 g, sodium bicarbonate 3.37 g and sodium sulfate anhydrous 11.37 g, as well as macrogol 4000, saccharin sodium hydrate, flavour as excipients. Niflec is dissolved in water to make approximately 2 L of solution before administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Efficacy Rate Based on the Overall Colon Cleansing Effect as Assessed by the Independent Central Judging Committee Using the Japanese Colon Cleansing Scale | The efficacy rate was based on the overall colon cleansing effect as assessed by the independent central judging committee: the rate of responders who were defined as subjects with a 1 or 2 rating in each colon segment on the Japanese colon cleansing scale, which has scale of 1 (Excellent observation) to 5 (Unable to judge). One of the 5 ratings to each of the colon segments (rectum, sigmoid colon, descending colon, transverse colon, and ascending colon/cecum) was given according to the description and the representative pictures of each rating. A subject who had a 1 or 2 rating in each colon segment was counted as a responder in the overall colon cleansing effect. Otherwise they were counted as a non-responder. | Day 1 (day of colonoscopy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Efficacy Rate Based on the Overall Colon Cleansing Effect Assessed by the Investigators at the Sites Using the Japanese Colon Cleansing Scale | The efficacy rate was based on the overall colon cleansing effect as assessed by the investigators at sites: the rate of responders who were defined as subjects with a 1 or 2 rating in each colon segment on the Japanese colon cleansing scale, which has scale of 1 (Excellent observation) to 5 (Unable to judge). One of the 5 ratings to each of the colon segments (rectum, sigmoid colon, descending colon, transverse colon, and ascending colon/cecum) was given according to the description and the representative pictures of each rating. A subject who had a 1 or 2 rating in each colon segment was counted as a responder in the overall colon cleansing effect. Otherwise they were counted as a non-responder. | Day 1 (day of colonoscopy) | 
| The Total Scores of the Colon Cleansing Effect by the Investigators at Sites Using the Ottawa Scale | The total Ottawa scale score was calculated by adding the ratings (0 to 4) for each of the three colon segments, Ascending colon (ascending, cecum), Mid colon (transverse, descending), and Recto-sigmoid colon, in addition to the overall fluid quantity rating (0 (small), 1 (medium), or 2 (large) ). This gave a sum of 0 (best) to 12 (worst) for overall assessment of colon cleansing, and an additional 0 to 2 for the global fluid quantity rating. The final range of the score was from 0 (excellent) to 14 (solid stool in each colon segment and lots of fluid). | Day 1 (day of colonoscopy) | 
| Evaluation of Acceptability of the Investigational Medicinal Products (IMPs) by Subjects Using a Questionnaire | The mean score of subjects who gave favourable impression on their assigned IMPs with 3 or 5 points scales, and the frequency of the response for yes/no questions was summarized in each of question for each treatment arm. Ease of consuming the assigned IMPs with a scale of 1(Very easy) to 5 (Very difficult) Overall impression of the assigned IMPs with a scale of 1(Excellent) to 5 (Bad) Taste of the assigned IMPs with a scale of 1 (Excellent) to 5 (Bad) Volume of the assigned IMPs with a scale of 1(Very much) to 3 (No problem) Impression of the assigned IMPs compared with other colon cleansing products with a scale of 1 (Much better) to 5 (Much worse) | Day 0 - Day 1 | 
| Evaluation of Acceptability of the Investigational Medicinal Products (IMPs) by Subjects Using a Questionnaire | The frequency of the response for yes/no questions was summarized in each of question for each treatment arm. Whether or not a subject will request for the assigned IMPs again when the next colonoscopy is needed, with yes-or-no answer Whether or not a subject will refuse the assigned IMPs when it is prescribed for the next colonoscopy, with yes-or-no answer | Day 0 - Day 1 |