Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus a Sodium Picosulfate and Magnesium Salt Solution Using Day Before-Only Dosing Regimen in Adults.

NCT02273141 | Completed Phase 3 Results

• 1 other identifier: NER1006-03/2014 (DAYB)
• Study Type: interventional
• Target: 515
• Locations: 6 countries
• Sites: 19

Brief Summary

This study evaluates the efficacy, safety and tolerability of NER1006 versus a sodium picosulfate and magnesium salt solution (SP + MS) in adult patients requiring bowel cleansing prior to any procedure that requires a clean bowel, using a Day Before Only Dosing regimen. Approximately 484 patients will be randomised with the aim of achieving a minimum of 220 patients in each of the 2 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 versus SP+MS was evaluated using a non-inferiority study design.

  One day (day before 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 SP+MS was evaluated using a non-inferiority study design.

  One day (day before colonoscopy)

Secondary Outcomes (4)

• Adenoma Detection Rate (Colon Ascendens)

  One day (day before colonoscopy).

• Adenoma Detection Rate (Overall Colon)

  One day (day before colonoscopy)

• Polyp Detection Rate (Colon Ascendens)

  One day (day before colonoscopy)

• Polyp Detection Rate (Overall Colon)

  One day (day before colonoscopy)

Study Arms (2)

NER1006, Day Before-Only Dosing

EXPERIMENTAL

NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).

Drug: NER1006, Day Before-Only Dosing

SP+MS, Day Before-Only Dosing

ACTIVE COMPARATOR

SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).

Drug: SP+MS, Day Before-Only Dosing

Interventions

NER1006, Day Before-Only Dosing DRUG

The subject will self-administer both doses of NER1006 in the evening of Day 1 with 1-2 hours interval. Subject will take mandatory additional clear fluid after each dose.

NER1006, Day Before-Only Dosing

SP+MS, Day Before-Only Dosing DRUG

The subject will self-administer SP+MS in the morning of Day 1 and afternoon of Day 1. Subject will take mandatory additional clear fluid after each dose.

SP+MS, Day Before-Only 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, able and competent 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), sodium picosulfate and magnesium salt compounds, 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 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 (19)

Charité - Campus Virchow Klinikum

Berlin, Germany

Location

University Hospital Schleswig-Holstein

Kiel, 24105, Germany

Location

An der Germania Brauerei 6

Münster, Germany

Location

An der Germania Brauerei 6

Milan, Italy

Location

Osp.San Raffaele U.O. Gastroenterologia

Milan, Italy

Location

P.T.P.Nuovo Regina Margherita

Rome, Italy

Location

Onze Lieve Vrouwe Gashuis

Amsterdam, Netherlands

Location

Albert Schweitzer Ziekenhuis

Dordrecht, Netherlands

Location

Radboud UMC

Nijmegen, Netherlands

Location

Orbis Medisch Centrum

Sittard, Netherlands

Location

Centrum Medyczne sw. Lukasza

Częstochowa, Poland

Location

Instytut Medycyny Wsi im. Witolda Chodzki w

Lubliniec, Poland

Location

Specjalistyczna Praktyka Lekarska dr med. Marek Horynski

Sopot, Poland

Location

SPSK Nr 1 im. Prof. Tadeusza Sokolowskiego

Szczecin, Poland

Location

Hospital de Vinalopó, Unidad de Endoscopia Digestiva

Elche, Spain

Location

Hospital Universitario de la Princesa

Madrid, Spain

Location

Hospital Universitario La Paz, Unidad Enfermedad Intestinal

Madrid, Spain

Location

Department of Surgery, Raigmore Hospital

Inverness, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

Related Publications (1)

• 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

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 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

• Stefan Schreiber

  University Hospital Schleswig-Holstein

  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: November 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

Locations

NL (4); PL (4); ES (3); DE (3); IT (3); GB (2)