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

Colon Cancer Clinical Trial

— NOCT  

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 a Trisulfate Bowel Cleansing Solution Using 2-Day Split-Dosing Regimen in Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02254486
• Other study ID #: NER1006-01/2014 (NOCT)
• Secondary ID: 29672
• Status: Completed
• Phase: Phase 3
• Start date: September 2014
• Est. completion date: June 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 621
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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.

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 (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.

• 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, in the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures, e.g. cognitively impaired, debilitated or fragile patients.

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• NER1006
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
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.

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials	Anaheim	California
United States	Investigative Clinical Research	Annapolis	Maryland
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	MGG Group Co., Inc., Chevy Chase Clinical	Chevy Chase	Maryland
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	Cumberland Research Associates, LLC	Fayetteville	North Carolina
United States	Long Island Gastrointestinal Research Group, LLP	Great Neck	New York
United States	Peters Medical Research	High Point	North Carolina
United States	Investigative Clinical Research, LLC	Mentor	Ohio
United States	Advanced Research Institute	Ogden	Utah
United States	Wake Research Associates, LLC	Raleigh	North Carolina
United States	Trial Management Associates, LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Norgine

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

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 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)
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 versus Trisulfate Solution was evaluated using a non-inferiority study design.	Two 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 is used for bowel cleansing versus Trisulfate Solution. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the colon ascendens.	Two 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 is used for bowel cleansing versus Trisulfate Solution. ADR defined as the number of patients with at least one adenoma in the overall colon.	Two 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 is used for bowel cleansing versus Trisulfate Solution. Polyp detection rate (PDR) defined as the number of patients with at least one polyp in the colon ascendens.	Two 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 Trisulfate Solution. PDR defined as the number of patients with at least one polyp in the overall colon.	Two days (from day of first dosing to day of colonoscopy)