Clinical trial NCT02254486: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colon Cancer
Colorectal Carcinoma
Colon Cleansing
Lead sponsor: Norgine
Sponsor class: INDUSTRY
First posted: 2014-10-02
Enrollment: 621
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With Successful Bowel Cleansing (Overall Colon)
timeFrame: Two days (from day of first dosing to day of colonoscopy)
measure: Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens)
timeFrame: Two days (from day of first dosing to day of colonoscopy)
Secondary outcomes:
measure: Adenoma Detection Rate (Colon Ascendens)
timeFrame: Two days (from day of first dosing to day of colonoscopy)
measure: Adenoma Detection Rate (Overall Colon)
timeFrame: Two days (from day of first dosing to day of colonoscopy)
measure: Polyp Detection Rate (Colon Ascendens)
timeFrame: Two days (from day of first dosing to day of colonoscopy)
measure: Polyp Detection Rate (Overall Colon)
timeFrame: Two days (from day of first dosing to day of colonoscopy)
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials
state: California
city: Annapolis
country: United States
facility: Investigative Clinical Research
state: Maryland
city: Chevy Chase
country: United States
facility: MGG Group Co., Inc., Chevy Chase Clinical
state: Maryland
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Great Neck
country: United States
facility: Long Island Gastrointestinal Research Group, LLP
state: New York
city: Fayetteville
country: United States
facility: Cumberland Research Associates, LLC
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Mentor
country: United States
facility: Investigative Clinical Research, LLC
state: Ohio
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
Study officials:
affiliation: Anaheim Clinical Trials, CA
name: Michael Demicco
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.