Clinical trial NCT02273141: 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.
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 Sodium Picosulfate and Magnesium Salt (SP+MS) Solution Using Day Before-Only Dosing Regimen in Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Colorectal Carcinoma
Colon Cleansing
Lead sponsor: Norgine
Sponsor class: INDUSTRY
First posted: 2014-10-23
Enrollment: 515
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 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.


Eligibility criteria: 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, able and competent 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), 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.
* 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.
* Patients with history of rhabdomyolysis

Primary outcomes:
measure: Number of Patients With Successful Bowel Cleansing (Overall Colon)
timeFrame: One day (day before colonoscopy)
measure: Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens)
timeFrame: One day (day before colonoscopy)
Secondary outcomes:
measure: Adenoma Detection Rate (Colon Ascendens)
timeFrame: One day (day before colonoscopy).
measure: Adenoma Detection Rate (Overall Colon)
timeFrame: One day (day before colonoscopy)
measure: Polyp Detection Rate (Colon Ascendens)
timeFrame: One day (day before colonoscopy)
measure: Polyp Detection Rate (Overall Colon)
timeFrame: One day (day before colonoscopy)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Campus Virchow Klinikum
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
city: Münster
country: Germany
facility: An der Germania Brauerei 6
city: Milan
country: Italy
facility: An der Germania Brauerei 6
city: Milan
country: Italy
facility: Osp.San Raffaele U.O. Gastroenterologia
city: Rome
country: Italy
facility: P.T.P.Nuovo Regina Margherita
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gashuis
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Sittard
country: Netherlands
facility: Orbis Medisch Centrum
city: Czestochowa
country: Poland
facility: Centrum Medyczne sw. Lukasza
city: Lubliniec
country: Poland
facility: Instytut Medycyny Wsi im. Witolda Chodzki w
city: Sopot
country: Poland
facility: Specjalistyczna Praktyka Lekarska dr med. Marek Horynski
city: Szczecin
country: Poland
facility: SPSK Nr 1 im. Prof. Tadeusza Sokolowskiego
city: Elche
country: Spain
facility: Hospital de Vinalopó, Unidad de Endoscopia Digestiva
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Unidad Enfermedad Intestinal
city: Inverness
country: United Kingdom
facility: Department of Surgery, Raigmore Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: University Hospital Schleswig-Holstein
name: Stefan Schreiber
role: PRINCIPAL_INVESTIGATOR
References:
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.