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 (NOCT)

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

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.

Study Overview

• Status: Completed
• Conditions: Colon Cancer; Colorectal Carcinoma; Colon Cleansing
• Intervention / Treatment: Drug: NER1006; Drug: Trisulfate solution

• Study Type: Interventional
• Enrollment (Actual): 621
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Investigative Clinical Research
    • Chevy Chase, Maryland, United States, 20815
      • MGG Group Co., Inc., Chevy Chase Clinical
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
  • New York
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group, LLP
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Cumberland Research Associates, LLC
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Wilmington, North Carolina, United States, 24803
      • Trial Management Associates, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research
    • Mentor, Ohio, United States, 44060
      • Investigative Clinical Research, LLC
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NER1006, 2-Day Split-Dosing; NER1006:2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)	Drug: NER1006; 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.
Active Comparator: Trisulfate Solution, 2-Day Split-Dosing; Trisulfate Solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)	Drug: Trisulfate solution; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Norgine
• Investigators: Principal Investigator: Michael Demicco, Anaheim Clinical Trials, CA

Publications and helpful links

General Publications

• DeMicco MP, Clayton LB, Pilot J, Epstein MS; NOCT Study Group. Novel 1 L polyethylene glycol-based bowel preparation NER1006 for overall and right-sided colon cleansing: a randomized controlled phase 3 trial versus trisulfate. Gastrointest Endosc. 2018 Mar;87(3):677-687.e3. doi: 10.1016/j.gie.2017.07.047. Epub 2017 Aug 10.
• Cash BD, Allen C, Poppers DM. Transient alterations in plasma sodium concentrations with NER1006 bowel preparation: an analysis of three phase III, randomized clinical trials. BMC Gastroenterol. 2022 Sep 5;22(1):412. doi: 10.1186/s12876-022-02484-7.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: October 1, 2014
• First Submitted That Met QC Criteria: October 1, 2014
• First Posted (Estimate): October 2, 2014

Study Record Updates

• Last Update Posted (Actual): May 15, 2018
• Last Update Submitted That Met QC Criteria: April 12, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: NER1006-01/2014 (NOCT); 29672 (Other Identifier: Quorum Review IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO