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

NCT02254486 | Completed Phase 3 Results

• 2 other identifiers: NER1006-01/2014 (NOCT)29672
• Study Type: interventional
• Target: 621
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Colon Cancer; Colorectal Carcinoma; Colon Cleansing

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Adenoma Detection Rate (Colon Ascendens)

  Two days (from day of first dosing to day of colonoscopy)

• Adenoma Detection Rate (Overall Colon)

  Two days (from day of first dosing to day of colonoscopy)

• Polyp Detection Rate (Colon Ascendens)

  Two days (from day of first dosing to day of colonoscopy)

• Polyp Detection Rate (Overall Colon)

  Two days (from day of first dosing to day of colonoscopy)

Study Arms (2)

NER1006, 2-Day Split-Dosing

EXPERIMENTAL

NER1006:2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)

Drug: NER1006

Trisulfate Solution, 2-Day Split-Dosing

ACTIVE COMPARATOR

Trisulfate Solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)

Drug: Trisulfate solution

Interventions

NER1006 DRUG

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.

NER1006, 2-Day Split-Dosing

Trisulfate solution DRUG

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.

Trisulfate Solution, 2-Day Split-Dosing

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Norgine: lead

Study Sites (12)

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

Investigative Clinical Research

Annapolis, Maryland, 21401, United States

Location

MGG Group Co., Inc., Chevy Chase Clinical

Chevy Chase, Maryland, 20815, United States

Location

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, 48047, United States

Location

Long Island Gastrointestinal Research Group, LLP

Great Neck, New York, 11023, United States

Location

Cumberland Research Associates, LLC

Fayetteville, North Carolina, 28304, United States

Location

Peters Medical Research

High Point, North Carolina, 27262, United States

Location

Wake Research Associates, LLC

Raleigh, North Carolina, 27612, United States

Location

Trial Management Associates, LLC

Wilmington, North Carolina, 24803, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45219, United States

Location

Investigative Clinical Research, LLC

Mentor, Ohio, 44060, United States

Location

Advanced Research Institute

Ogden, Utah, 84405, United States

Location

Related Publications (2)

• 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.

  PMID: 28803744 BACKGROUND

• 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.

  PMID: 36064325 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Limitations and Caveats

Imputation of failure occurred in 7% of patients. This strict analytical approach reduced the cleansing success rates for both treatments.

Results Point of Contact

• Title: Lucy Clayton
• Organization: Norgine Ltd

lclayton@norgine.com

+44-1895-826669

Study Officials

• Michael Demicco

  Anaheim Clinical Trials, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: October 2, 2014
• Study Start: September 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: May 15, 2018
• Results First Posted: May 23, 2017

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)