| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Bowel cleansing prior to any procedure that requires a clean bowel, e.g. colonoscopy, surgical, video capsule or radiological procedures. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Bowel cleansing prior to colonoscopy |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10066943 |
| E.1.2 | Term | Bowel preparation |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the overall bowel cleansing efficacy and the ‘Excellent plus Good’ cleansing rate in the colon ascendens of 2-day split-dosing and 1-day morning of colonoscopy split-dosing regimens with NER1006 compared to a 2-day split-dosing regimen with MOVIPREP®, graded according to the Harefield Cleansing Scale© (HCS©) in patients undergoing screening, surveillance or diagnostic colonoscopy. |
|
| E.2.2 | Secondary objectives of the trial |
1.To assess the Adenoma Detection Rate (ADR) with NER1006 compared to MOVIPREP® for the colon ascendens.
2.To assess the overall ADR with NER1006 compared to MOVIPREP®.
3.To assess the Polyp Detection Rate (PDR) with NER1006 compared to MOVIPREP® for the colon ascendens.
4.To assess the overall PDR with NER1006 compared to MOVIPREP®.
Supportive :
1.To evaluate the segmental bowel cleansing efficacy of NER1006 compared to MOVIPREP®, graded according to the HCS in patients undergoing screening, surveillance or diagnostic colonoscopy for each of the other four colon segments (colon transversum, colon descendens, colon sigmoidum and rectum).
2.To assess the bowel cleansing quality with NER1006 compared to MOVIPREP® using the Boston Bowel Preparation Scale (BBPS).
3.To assess tolerability using PRO(BOCLIR).NB latter for use in the US and UK only
4.To assess patient compliance and acceptability using PRO.
Safety Objective:
To evaluate the safety of NER1006 compared to MOVIPREP®.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients will be entered into this study only if they satisfy the following criteria:
1.Patients must provide written informed consent.
2.Male and female outpatients and inpatients aged: ≥18 to ≤85 years undergoing a screening, surveillance or diagnostic colonoscopy.
3.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).
*A female condom and a male condom should not be used together as friction
between the two can result in either product failing.
If any female patient has a positive pregnancy test at Visit 2, they will be excluded
from further participation in the study for the efficacy evaluation, i.e. they will not
undergo the colonoscopy procedure. The Investigator will be required to arrange a
colonoscopy procedure outside of the study.
Note: The above birth control methods do not apply to females who are postmenopausal
or surgically sterile i.e. 12 months of natural (spontaneous) amenorrhea
or 6 weeks’ post-surgical bilateral oophorectomy with or without hysterectomy or
hysterectomy, or whose sole sexual partner has had a vasectomy and has received
medical assessment of the surgical success.
4.Willing, able and competent to complete the entire study and to comply with instructions.
|
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from this study if they meet any of the following criteria:
1.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.
2.Patients with ongoing severe acute Inflammatory Bowel Disease (IBD).
3.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.
4.Regular use of laxatives or colon motility altering drugs in the last month (i.e. more
than 2-3 times per week) in the last 28 days prior to the Screening Visit and/or
laxative use within 72 hours prior to administration of the preparation.
5.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.
6.Known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
7.Known phenylketonuria.
8.Known hypersensitivity to polyethylene glycols, ascorbic acid and sulfates (not
including sulfa-based products) or any other component of the investigational
product or comparator.
9.Past history within the last 12 months or evidence of any on-going clinically relevant electrocardiogram (ECG) abnormalities (e.g. arrhythmias).
10.History of uncontrolled hypertension with systolic blood pressure >170 mmHg and diastolic blood pressure >100 mmHg.
11.Patients with cardiac insufficiency NYHA grades III or IV.
12.Patients with severe renal insufficiency (i.e. with GFR, <30 mL/min/1.73m2).
13.Patient with serum albumin < 3.4 g/dL.
14.Patients with known liver disease of grades B and C according to the Child Pugh
classification.
15.Patients suffering from dehydration at screening as evaluated by the Investigator from physical examination and laboratory investigations.
16.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.
17.Patients with any other clinically significant hematological parameters including coagulation profile at screening.
18.Patients with impaired consciousness that might predispose them to pulmonary aspiration.
19.Patients undergoing colonoscopy for foreign body removal and/or decompression.
20.Patients who are pregnant or lactating, or intending to become pregnant during the study.
21.Clinically relevant findings on physical examination based on the Investigator’s judgment.
22.History of drug or alcohol abuse within the 12 months prior to dosing.
23.Concurrent participation in an investigational drug or device study or participation within three months of study entry.
24.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.
25.Patients who are ordered to live in an institution on court or authority order.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1.The overall bowel cleansing success rate of NER1006 is non-inferior to that of MOVIPREP® using the HCS, wherein success corresponds to Grades A and B, and failure corresponds to Grades C and D.
2.The ‘Excellent plus Good’ cleansing rate in the colon ascendens of NER1006 is non-inferior to that of MOVIPREP® using the segmental cleansing scoring system of the HCS, wherein the ordinal score of 4 corresponds to ‘Excellent’ cleansing and score of 3 corresponds to ‘Good’ cleansing.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Cleansing success rate : During colonoscopy |
|
| E.5.2 | Secondary end point(s) |
Key secondary endpoints:
•ADR as defined by the proportion of patients with at least one adenoma in the colon ascendens as confirmed by a pathologist.
•ADR as defined by the proportion of patients with at least one adenoma in the overall colon as confirmed by a pathologist.
•PDR as defined by the proportion of patients with at least one polyp in the colon ascendens, as confirmed by the colonoscopist.
•PDR as defined by the proportion of patients with at least one polyp in the overall colon as confirmed by the colonoscopist.
Supportive secondary endpoints:
•The ‘Excellent plus Good’ cleansing rate for the other four colon segments (colon transversum, colon descendens, colon sigmoidum and rectum) using the HCS.
•Bowel cleansing success rates using the Boston Bowel Preparation Scale.
•Tolerability as assessed using PRO (BOCLIR where applicable).
•Compliance and acceptability as assessed using PRO.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Segmental cleansing score : During colonoscopy |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belgium |
| France |
| Germany |
| Italy |
| Netherlands |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
Print
