Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus Trisulfate Solution Using 2-Day Split-Dosing Regimen in Adults

Study Overview
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Brief Summary
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This study evaluates the efficacy, safety and tolerability of NER1006 versus Trisulfate Solution (TS) in adult patients requiring bowel cleansing prior to any procedure that requires a clean bowel, using a 2-Day evening/morning Split-Dosing regimen. Approximately 540 patients will be randomised with the aim of achieving a minimum of 245 patients in each of the 2 groups.

Official Title
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A Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 (a Low Volume Bowel Cleansing Solution) Versus a Trisulfate Bowel Cleansing Solution Using 2-Day Split-Dosing Regimen in Adults

Conditions
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Colon Cancer, Colorectal Carcinoma, Colon Cleansing

Intervention / Treatment
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* Drug: NER1006
* Drug: Trisulfate solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Male and female outpatients and inpatients aged ≥18 to ≤85 years undergoing a screening, surveillance, or diagnostic colonoscopy Females of child bearing potential must have a negative pregnancy test at Screening and at Visit 2 and must be practising one of the following methods of birth control and agree to continue with the regimen throughout the study period: Oral, implantable, or injectable contraceptives (for a minimum of three months before study entry) in combination with a condom; Intrauterine device in combination with a condom; Double barrier method (condom* and occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository) Willing, able and competent to complete study and comply with instructions. Exclusion Criteria: Patients with past history within last 12 months or current episode of severe constipation (requiring repeated use of laxatives/enema or physical intervention before resolution), known or suspected ileus, gastrointestinal obstruction, gastric retention, bowel perforation, toxic colitis or megacolon. Patients with ongoing severe acute Inflammatory Bowel Disease (IBD). Patients who have had previous significant gastrointestinal surgeries, including colonic resection, sub-total colectomy, abdomino-perineal resection, de-functioning colostomy, Hartmann's procedure and de-functioning ileostomy or other similar surgeries involving structure and function of the small or large colon. Regular use of laxatives or colon motility altering drugs in the last month (i.e. more than 2-3 times per week) and/or laxative use within 72 hours prior to administration of the preparation. Patients with active intestinal bleeding episodes or with a clinically significant low hemoglobin level <9 g/dL for women and <11 g/dL for men at screening. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency. Known phenylketonuria. Known hypersensitivity to polyethylene glycols, ascorbic acid and sulfates (not including sulfa-based products) or any other component of the investigational product or comparator. Past history within the last 12 months or evidence of any on-going clinically relevant electrocardiogram (ECG) abnormalities (e.g. arrhythmias). History of uncontrolled hypertension with systolic blood pressure >170 mmHg and diastolic blood pressure >100 mmHg. Patients with cardiac insufficiency NYHA grades III or IV. Patients with moderate to severe renal insufficiency (i.e. with GFR, <60 mL/min/1.73m2). Patient with serum albumin < 3.4 g/dL. Patients with liver disease of grades B and C according to the Child Pugh classification. Patients suffering from dehydration at screening as evaluated by the Investigator from physical examination and laboratory investigations. Patients with clinically significant electrolyte abnormalities, whether pre-existing or noted at screening, such as hypernatremia, hyponatremia, hyperphosphatemia, hypermagnesemia, hypokalemia, hypocalcaemia, dehydration, or those secondary to the use of diuretics or angiotensin converting enzyme (ACE) inhibitors. Patients with any other clinically significant hematological parameters including coagulation profile at screening. Patients with impaired consciousness that might predispose them to pulmonary aspiration. Patients undergoing colonoscopy for foreign body removal and/or decompression. Patients who are pregnant or lactating, or intending to become pregnant during the study. Clinically relevant findings on physical examination based on the Investigator's judgment. History of drug or alcohol abuse within the 12 months prior to dosing. Concurrent participation in an investigational drug or device study or participation within three months of study entry. Patients who, in the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures, e.g. cognitively impaired, debilitated or fragile patients. Patients who are ordered to live in an institution on court or authority order.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NER1006, 2-Day Split-Dosing<br>NER1006:2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy) | Drug: NER1006<br>* The subject will self-administer the first dose of the assigned investigational product in the evening prior to the scheduled colonoscopy and take mandatory additional clear fluid. Subject will take the second dose together with mandatory additional clear fluids on the morning of the colonoscopy.<br>|
| Active Comparator: Trisulfate Solution, 2-Day Split-Dosing<br>Trisulfate Solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy) | Drug: Trisulfate solution<br>* The subject will self-administer the first dose of the assigned investigational product in the evening prior to the scheduled colonoscopy and take mandatory additional clear fluid. Subject will take the second dose together with mandatory additional clear fluids on the morning of the colonoscopy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Successful Bowel Cleansing (Overall Colon) | The overall quality of bowel cleansing was assessed by a blinded central reader (an experienced and trained colonoscopist) using the segmental scores of the Harefield Cleansing Scale (HCS). A final HCS grading of A, B, C or D was derived. Grades A and B are classified as successful (i.e., all mucosa could be visualised) and C and D are classified as unsuccessful. Comparison of overall success of cleansing with NER1006 versus Trisulfate solution was evaluated using a non-inferiority study design. | Two days (from day of first dosing to day of colonoscopy) | 
| Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens) | The overall quality of bowel cleansing was assessed by a blinded central reader (an experienced and trained colonoscopist) using the segmental scores of the Harefield Cleansing Scale (HCS). Highly effective cleansing in the colon ascendens corresponded to scores 3 (Good) or 4 (Excellent) of the HCS. Adequate plus failure of cleansing corresponded to score 0-2. Comparison of 'Excellent plus good' cleansing of the colon ascendens using NER1006 versus Trisulfate Solution was evaluated using a non-inferiority study design. | Two days (from day of first dosing to day of colonoscopy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adenoma Detection Rate (Colon Ascendens) | Comparison of the number of patients with at least one adenoma detected in the colon ascendens when NER1006 is used for bowel cleansing versus Trisulfate Solution. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the colon ascendens. | Two days (from day of first dosing to day of colonoscopy) | 
| Adenoma Detection Rate (Overall Colon) | Comparison of the number of patients with at least one adenoma detected in the overall colon when NER1006 is used for bowel cleansing versus Trisulfate Solution. ADR defined as the number of patients with at least one adenoma in the overall colon. | Two days (from day of first dosing to day of colonoscopy) | 
| Polyp Detection Rate (Colon Ascendens) | Comparison of the number of patients with at least one polyp detected in the colon ascendens when NER1006 is used for bowel cleansing versus Trisulfate Solution. Polyp detection rate (PDR) defined as the number of patients with at least one polyp in the colon ascendens. | Two days (from day of first dosing to day of colonoscopy) | 
| Polyp Detection Rate (Overall Colon) | Comparison of the number of patients with at least one polyp detected in the overall colon when NER1006 is used for bowel cleansing versus Trisulfate Solution. PDR defined as the number of patients with at least one polyp in the overall colon. | Two days (from day of first dosing to day of colonoscopy) |