Endoscopy 2019; 51(01): 60-72
DOI: 10.1055/a-0638-8125
Original article
© Georg Thieme Verlag KG Stuttgart · New York

Colon cleansing efficacy and safety with 1 L NER1006 versus 2 L polyethylene glycol + ascorbate: a randomized phase 3 trial

Raf Bisschops
1   KU Leuven, University Hospitals Leuven, Leuven, Belgium
Jonathan Manning
2   Borders General Hospital, NHS Borders, Melrose, United Kingdom
Lucy B. Clayton
3   Clinical Development, Norgine Ltd, Harefield, United Kingdom
Richard Ng Kwet Shing
3   Clinical Development, Norgine Ltd, Harefield, United Kingdom
Marco Álvarez-González
4   Hospital del Mar, Barcelona, Spain
on behalf of the MORA Study Group › Author Affiliations
TRIAL REGISTRATION: Multicenter, randomized, parallel group, phase 3 trial NCT02273167 at clinicaltrials.gov
Further Information

Publication History

submitted 19 December 2017

accepted after revision 30 April 2018

Publication Date:
19 July 2018 (online)


Background Polyethylene glycol (PEG)-based bowel preparations are effective cleansers but many require high-volume intake. This phase 3, randomized, blinded, multicenter, parallel-group, central reader-assessed study assessed the 1 L PEG NER1006 bowel preparation vs. standard 2 L PEG with ascorbate (2LPEG).

Methods Patients undergoing colonoscopy were randomized (1:1:1) to receive NER1006, as an evening/morning (N2D) or morning-only (N1D) regimen, or evening/morning 2LPEG. Cleansing was assessed using the Harefield Cleansing Scale (HCS) and the Boston Bowel Preparation Scale (BBPS). Primary end points were overall bowel cleansing success and high-quality cleansing in the right colon. Modified full analysis set (mFAS) and per protocol (PP) analyses were performed. Mean cleansing scores were analyzed post hoc.

Results Of 849 randomized patients, efficacy was analyzed in the following patient numbers (mFAS/PP): total n = 822/670; N2D n = 275/220; N1D n = 275/218; 2LPEG n = 272/232. mFAS established noninferiority. PP showed superiority for N2D on overall success (97.3 % vs. 92.2 %; P = 0.014), and for N2D and N1D on right colon high-quality cleansing (N2D 32.3 % vs. 15.9 %, P < 0.001; N1D 34.4 % vs. 15.9 %, P < 0.001) vs. 2LPEG. Using HCS, N2D and N1D attained superior segmental high-quality cleansing (P ≤ 0.003 per segment). N2D showed superior mean segmental HCS scores (P ≤ 0.007 per segment). Both N2D and N1D achieved superior mean overall (P < 0.001 and P = 0.006) and right colon BBPS scores (P < 0.001 and P = 0.013). N2D demonstrated superior right colon polyp detection (P = 0.024). Adherence, tolerability, and safety were comparable between treatments.

Conclusions NER1006 is the first low-volume preparation to demonstrate superior colon cleansing efficacy vs. standard 2LPEG with ascorbate, with comparable safety and tolerability.

European Clinical Trials Database (EudraCT)
TRIAL REGISTRATION: Multicenter, randomized, parallel group, phase 3 trial 2014-002185-78 at https://eudract.ema.europa.eu/

Table e1 – e3, Table e5, Table e7, Fig. e5 and Fig. e6

  • References

  • 1 Levin B, Lieberman DA, McFarland B. et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology 2008; 134: 1570-1595
  • 2 Belsey J, Epstein O, Heresbach D. Systematic review: oral bowel preparation for colonoscopy. Aliment Pharmacol Ther 2007; 25: 373-384
  • 3 Menees SB, Elliott E, Govani S. et al. The impact of bowel cleansing on follow-up recommendations in average-risk patients with a normal colonoscopy. Am J Gastroenterol 2014; 109: 148-154
  • 4 Hassan C, Bretthauer M, Kaminski MF. et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2013; 45: 142-150
  • 5 Clark BT, Laine L. High-quality bowel preparation is required for detection of sessile serrated polyps. Clin Gastroenterol Hepatol 2016; 14: 1155-1162
  • 6 Rex DK, Ahnen DJ, Baron JA. et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012; 107: 1315-1329
  • 7 Bechtold ML, Mir F, Puli SR. et al. Optimizing bowel preparation for colonoscopy: a guide to enhance quality of visualization. Ann Gastroenterol 2016; 29: 137-146
  • 8 Belsey J, Crosta C, Epstein O. et al. Meta-analysis: the relative efficacy of oral bowel preparations for colonoscopy 1985–2010. Aliment Pharmacol Ther 2012; 35: 222-237
  • 9 Ell C, Fischbach W, Bronisch H-J. et al. Randomized trial of low-volume PEG solution versus standard PEG + electrolytes for bowel cleansing before colonoscopy. Am J Gastroenterol 2008; 103: 883-893
  • 10 Worthington J, Thyssen M, Chapman G. et al. A randomised controlled trial of a new 2 litre polyethylene glycol solution versus sodium picosulphate + magnesium citrate solution for bowel cleansing prior to colonoscopy. Curr Med Res Opin 2008; 24: 481-488
  • 11 Halphen M, Tayo B, Flanagan S. et al. Pharmacodynamic and clinical evaluation of low-volume polyethylene glycol (PEG)-based bowel cleansing solutions (NER1006) using split dosing in healthy and screening colonoscopy subjects. Am J Gastroenterol 2014; 109: S189
  • 12 Bisschops R, Manning J, Clayton L. et al. Efficacy and safety of the novel 1L PEG and ascorbate bowel preparation NER1006 versus standard 2L PEG with ascorbate in overnight or morning split-dosing administration: results from the phase 3 study MORA. Gastroenterology 2016; 150: S1269-S1270
  • 13 DeMicco MP, Clayton LB, Pilot J. et al. 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; 87: 677-687.e3
  • 14 Schreiber S, Baumgart DC, Drenth JPH. et al. Colon cleansing efficacy and safety with 1 L NER1006 versus sodium picosulfate with magnesium citrate: a randomized phase 3 trial. Endoscopy 2019; 51 DOI: 10.1055/a-0639-5070.
  • 15 European Medicines Agency. EMA/CHMP/336243/2013. Guideline on the evaluation of medicinal products for the treatment of chronic constipation (including opioid induced constipation) and for bowel cleansing. 25.06.2015 Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/09/WC500193391.pdf
  • 16 Halphen M, Heresbach D, Gruss H-J. et al. Validation of the Harefield Cleansing Scale: a tool for the evaluation of bowel cleansing quality in both research and clinical practice. Gastrointest Endosc 2013; 78: 121-131
  • 17 Lai EJ, Calderwood AH, Doros G. et al. The Boston Bowel Preparation Scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc 2009; 69: 620-625
  • 18 Parmar R, Martel M, Rostom A. et al. Validated scales for colon cleansing: a systematic review. Am J Gastroenterol 2016; 111: 197-204
  • 19 Johnson DA, Barkun AN, Cohen LB. et al. Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2014; 147: 903-924
  • 20 Kaminski M, Thomas-Gibson S, Bugajski M. et al. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy 2017; 49: 378-397
  • 21 Corley DA, Jensen CD, Marks AR. et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014; 370: 1298-1306
  • 22 Kaminski MF, Wieszczy P, Rupinski M. et al. Increased rate of adenoma detection associates with reduced risk of colorectal cancer and death. Gastroenterology 2017; 153: 98-105
  • 23 Lasisi F, Rex DK. Improving protection against proximal colon cancer by colonoscopy. Expert Rev Gastroenterol Hepatol 2011; 5: 745-754
  • 24 Hassan C, Manning J, Amlani B. et al. High-quality colon cleansing improves polyp and adenoma detection rates: post hoc analysis of 1749 patients in three randomized Phase 3 clinical trials. Am J Gastroenterol 2017; 112: S140
  • 25 Pontone S, Hassan C, Maselli R. et al. Multiple, zonal and multi-zone adenoma detection rates according to quality of cleansing during colonoscopy. United European Gastroenterol J 2016; 4: 778-783