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.

Colorectal Cancer Clinical Trial

— MORA  

Official title:

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 MOVIPREP Using 2-Day Split-Dosing and 1-Day Morning Split-Dosing Regimen in Adults.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02273167
• Other study ID #: NER1006-02/2014 (MORA)
• Status: Completed
• Phase: Phase 3
• Start date: October 2014
• Est. completion date: August 2015

Study information

• Verified date: April 2018
• Source: Norgine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 849
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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.

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.

• 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.

• 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 are ordered to live in an institution on court or authority order

Related Conditions & MeSH terms

• Colon Cleansing
• Colorectal Cancer
• Colorectal Carcinoma
• Colorectal Neoplasms

Intervention

Drug:
• NER1006, 2-Day Split-Dosing
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.
• NER1006,1-Day Morning Split-Dosing
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.
• MOVIPREP, 2-Day Split-Dosing
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.

Locations

Country	Name	City	State
Belgium	AZ Sint-Lucas	Brugge
Belgium	UZ Ghent	Ghent
Belgium	UZ Leuven	Leuven
Belgium	CHC- Clinique Saint-Joseph	Liège
France	Hôpital Avicenne- Service de Gastro-Entérologie	Bobigny
France	Hôpital Hotel-Dieu	Nantes
Germany	Kliniken Essen-Mitte; Abteilung für Gastroenterologie	Essen
Germany	Klinikum der Friedrich Schiller Universität Jena	Jena
Germany	Praxis für Innere Medizin, Gastroenterologie und Allg. Medizin	Ludwigshafen
Italy	A.O.U. di Bologna - Policlinico S. Orsola-Malpighi	Bologna
Italy	Ospedale Valduce U.O. Gastroenterologia e Endoscopia	Como
Italy	P.O. Maresca OORR Area Vesuviana ASL	Naples
Italy	Centro di Riferimento Oncologico (C.R.O.) S.O.C Gastroenterologia	Pordenone
Italy	Pol. Univ. A. Gemelli U.O. di Endoscopia Digestiva Chirurgica	Roma
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok
Poland	Gabinet Internistyczny dr n. med. Krzysztof Janik	Czestochowa
Poland	NZOZ Centrum Medyczne-Szpital Swietej Rodziny	Lódz
Poland	Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych	Warsaw
Poland	Robert Petryka Gabinet Internistyczny	Warsaw
Poland	Lexmedica Durbajlo Hanna	Wroclaw
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Ramon y Cajal - Ctra. De Colmenar km. 9, 100	Madrid
United Kingdom	Lothian Health Board	Edinburgh
United Kingdom	Borders General Hospital	Melrose
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury
United Kingdom	Royal Albert Edward Infirmary Department	Wigan

Sponsors (1)

Lead Sponsor	Collaborator
Norgine

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Adenoma Detection Rate (Colon Ascendens)	Comparison of the number of patients with at least one adenoma detected in the colon ascendens when NER1006 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the colon ascendens.	Up to 2 days (from day of first dosing to day of colonoscopy)
Secondary	Adenoma Detection Rate (Overall Colon)	Comparison of the number of patients with at least one adenoma detected in the overall colon when NER1006 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the overall colon.	Up to 2 days (from day of first dosing to day of colonoscopy)
Secondary	Polyp Detection Rate (Colon Ascendens)	Comparison of the number of patients with at least one polyp detected in the colon ascendens when NER1006 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Polyp detection rate (PDR) defined as the number of patients with at least one polyp in the colon ascendens.	Up to 2 days (from day of first dosing to day of colonoscopy)
Secondary	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 number detected when MOVIPREP is used. PDR defined as the number of patients with at least one polyp in the overall colon.	Up to 2 days (from day of first dosing to day of colonoscopy)