Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus MOVIPREP® Using 2-Day Split-Dosing and 1-Day Morning Split-Dosing Regimen in Adults.

NCT02273167 | Completed Phase 3 Results

• 1 other identifier: NER1006-02/2014 (MORA)
• Study Type: interventional
• Target: 849
• Locations: 7 countries
• Sites: 29

Brief Summary

This study evaluates the efficacy, safety and tolerability of NER1006 versus MOVIPREP in adult patients requiring bowel cleansing prior to any procedure that requires a clean bowel, using a 2-Day evening/morning Split-Dosing and 1-Day morning only Split-Dosing regimens. Approximately 810 patients will be randomised with the aim of achieving a minimum of 245 patients in each of the 3 groups.

Conditions

Colorectal 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 visualized) and C and D are classified as unsuccessful. Comparison of overall success of cleansing with NER1006 2-Day and 1-Day versus MOVIPREP was evaluated using a non-inferiority study design.

  Up to 2 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 2-Day and 1-Day versus MOVIPREP was evaluated using a non-inferiority study design.

  Up to 2 days (from day of first dosing to day of colonoscopy)

Secondary Outcomes (4)

• Adenoma Detection Rate (Colon Ascendens)

  Up to 2 days (from day of first dosing to day of colonoscopy)

• Adenoma Detection Rate (Overall Colon)

  Up to 2 days (from day of first dosing to day of colonoscopy)

• Polyp Detection Rate (Colon Ascendens)

  Up to 2 days (from day of first dosing to day of colonoscopy)

• Polyp Detection Rate (Overall Colon)

  Up to 2 days (from day of first dosing to day of colonoscopy)

Study Arms (3)

NER1006, 2-Day Split-Dosing

EXPERIMENTAL

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

Drug: NER1006, 2-Day Split-Dosing

NER1006,1-Day Morning Split-Dosing

EXPERIMENTAL

NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy).

Drug: NER1006,1-Day Morning Split-Dosing

MOVIPREP, 2-Day Split-Dosing

ACTIVE COMPARATOR

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

Drug: MOVIPREP, 2-Day Split-Dosing

Interventions

NER1006, 2-Day Split-Dosing 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

NER1006,1-Day Morning Split-Dosing DRUG

The subject will self-administer the first dose of the investigational product on the morning of the colonoscopy and take mandatory additional clear fluid. After a 1-2 hour break the subject will self-administer the second dose plus additional clear mandatory fluid.

NER1006,1-Day Morning Split-Dosing

MOVIPREP, 2-Day Split-Dosing DRUG

The subject will self-administer the first dose of the assigned investigational product in the evening prior to the scheduled colonoscopy and take recommended additional clear fluid. Subject will take the second dose together with recommended additional clear fluids on the morning of the colonoscopy.

MOVIPREP, 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:

• Patients must provide 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 (unless postmenopausal or surgically sterile, or whose sole sexual partner has had a successful vasectomy): 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 and able to complete the entire study and to 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.
• 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 study drug 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 severe renal insufficiency (i.e. with GFR, \<30 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 (29)

AZ Sint-Lucas

Bruges, Belgium

Location

UZ Ghent

Ghent, Belgium

Location

UZ Leuven

Leuven, 3000 Leuven, Belgium

Location

CHC- Clinique Saint-Joseph

Liège, Belgium

Location

Hôpital Avicenne- Service de Gastro-Entérologie

Bobigny, France

Location

Hôpital Hotel-Dieu

Nantes, France

Location

Kliniken Essen-Mitte; Abteilung für Gastroenterologie

Essen, Germany

Location

Klinikum der Friedrich Schiller Universität Jena

Jena, Germany

Location

Praxis für Innere Medizin, Gastroenterologie und Allg. Medizin

Ludwigshafen, Germany

Location

A.O.U. di Bologna - Policlinico S. Orsola-Malpighi

Bologna, Italy

Location

Ospedale Valduce U.O. Gastroenterologia e Endoscopia

Como, Italy

Location

P.O. Maresca OORR Area Vesuviana ASL

Naples, Italy

Location

Centro di Riferimento Oncologico (C.R.O.) S.O.C Gastroenterologia

Pordenone, Italy

Location

Pol. Univ. A. Gemelli U.O. di Endoscopia Digestiva Chirurgica

Roma, Italy

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, Poland

Location

Gabinet Internistyczny dr n. med. Krzysztof Janik

Częstochowa, Poland

Location

NZOZ Centrum Medyczne-Szpital Swietej Rodziny

Lodz, Poland

Location

Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych

Warsaw, Poland

Location

Robert Petryka Gabinet Internistyczny

Warsaw, Poland

Location

Lexmedica Durbajlo Hanna

Wroclaw, Poland

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Ramon y Cajal - Ctra. De Colmenar km. 9, 100

Madrid, Spain

Location

Lothian Health Board

Edinburgh, United Kingdom

Location

Borders General Hospital

Melrose, United Kingdom

Location

Royal Shrewsbury Hospital

Shrewsbury, United Kingdom

Location

Royal Albert Edward Infirmary Department

Wigan, United Kingdom

Location

Related Publications (2)

• 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

• Bisschops R, Manning J, Clayton LB, Ng Kwet Shing R, Alvarez-Gonzalez M; MORA Study Group. Colon cleansing efficacy and safety with 1 L NER1006 versus 2 L polyethylene glycol + ascorbate: a randomized phase 3 trial. Endoscopy. 2019 Jan;51(1):60-72. doi: 10.1055/a-0638-8125. Epub 2018 Jul 19.

  PMID: 30025414 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

MoviPrep

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 4% 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

• Raf Bisschops, MD

  UZ Leuven

  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 16, 2014
• First Posted: October 23, 2014
• Study Start: October 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: May 15, 2018
• Results First Posted: April 18, 2017

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); PL (6); GB (4); DE (3); BE (4); IT (5); ES (5)