| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subjects scheduled for elective colonoscopy to be prepared and performed according to ESGE (European Society of Gastrointestinal Endoscopy - ESGE) guidelines. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Subjects scheduled for elective colonoscopy. |
|
| E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10010007 |
| E.1.2 | Term | Colonoscopy |
| E.1.2 | System Organ Class | 10022891 - Investigations |
|
| 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 |
Phase II: Dose-finding/Pharmacokinetic sub-study:
- To determine the effective and safe dose of mannitol for adequate bowel cleansing to be used in the comparative non-inferiority phase of the study (phase III).
- To define the pharmacokinetic profile of the mannitol doses used in dose finding through a pharmacokinetic sub-study.
Phase III: Non-inferiority:
- To demonstrate the non-inferiority of mannitol vs. standard split 2L PEG ASC (Moviprep®) in bowel cleansing for colonoscopy.
- To assess the safety and tolerability of mannitol.
- To assess the adherence to and acceptability of the bowel preparation with mannitol and Moviprep®. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Pharmacokinetic sub-study (Phase II). |
|
| E.3 | Principal inclusion criteria |
1. Written informed consent
2. Age ≥ 18 years
3. Males and females scheduled for elective (screening, surveillance or diagnostic) colonoscopy to be prepared and performed according to the European Society of Gastrointestinal Endoscopy (ESGE) Guideline
4. Patients willing and able to complete the entire study and to comply with instructions. |
|
| E.4 | Principal exclusion criteria |
1. Pregnancy or breastfeeding. Females of childbearing potential must have a negative pregnancy test at Visit 2 and must practice one of the following methods of birth control 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 with spermicidal foam/gel/film/cream/suppository).
2. Severe renal failure: glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 estimated by means of simplified MDRD equation.
3. Severe heart failure: NYHA Class III-IV.
4. Severe anaemia (Hb ≤ 8 g/dl).
5. Ongoing severe acute Inflammatory Bowel Disease.
6. Chronic liver disease Child-Pugh class B or C.
7. Electrolyte disturbances (Na, Cl, K, Ca or P out of normal ranges).
8. Recent (< 6 months) symptomatic acute ischemic heart disease.
9. History of significant gastrointestinal surgeries, including colon resection, sub-total colectomy, abdominoperineal resection, de-functioning colostomy or ileostomy, Hartmann’s procedure and other surgeries involving the structure and function of the colon.
10. Use of laxatives, colon motility altering drugs and/or other substances (e.g. simethicone) that can affect bowel cleansing or visibility during colonoscopy within 24 hours prior to colonoscopy.
11. Suspected bowel obstruction or perforation.
12. Indication for partial colonoscopy.
13. Patients who have received an investigational drug or therapy within 5 half-lives of the first visit.
14. Patients previously screened for participation in this study.
15. Hypersensitivity to the active ingredients or to any of the excipients of the study drugs.
16. Contraindication to Moviprep® (only for phase III). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase II - Dose finding:
1. Primary efficacy endpoint: proportion of patients with adequate bowel cleansing, defined as Boston Bowel Preparation Scale (BBPS) total score ≥ 6, with a score for each of the three colon segments (right; transverse, including flexures; and left, including sigmoid and rectum) ≥ 2.
Phase III - Non-inferiority:
2. Primary efficacy endpoint: proportion of patients with adequate bowel cleansing: BBPS total score ≥ 6, with a score for each of the three colon segments (right; transverse, including flexures; and left, including sigmoid and rectum) ≥ 2. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. during colonoscopy after standard washing and air insufflation for luminal distension.
2. during colonoscopy after standard washing and air insufflation for luminal distension. |
|
| E.5.2 | Secondary end point(s) |
Phase II - Dose finding:
1. Secondary efficacy endpoint: caecal intubation rate, defined as the percentage of patients with appendiceal orifice visible to the endoscopist.
2. Safety and tolerability
a. Proportion of patients in safe conditions, defined as the absence in each colon segment (right, between ileocecal valve and appendix or as close as possible to the ileocecal valve in case of obstacles that prevent reaching the valve; transverse, including flexures; and left at the sigmoidal-rectum junction, 15-25 cm from anal margin) of potentially dangerous levels of H2 and/or CH4 (> 4% and > 5% respectively).
b. Incidence of adverse events.
c. Proportion of patients with change from baseline considered clinically significant by the Investigator of haematological and chemical parameters (CBC, creatinine, BUN, eGFR, ALT, AST, glucose, electrolytes).
d. Proportion of patients with change from baseline considered clinically significant by the Investigator of vital signs (heart rate, systolic and diastolic blood pressure).
3. Adherence and acceptability
a. Adherence: study drug completely taken, partially taken, not taken.
b. Ease of use: numeric rating scale (NRS) (0 = very difficult to 10 = very easy).
c. Taste: NRS (0 = terrible to 10 = very good).
d. Willingness to reuse the preparation (yes/no).
Phase II - Pharmacokinetic sub-study:
• Cmax: maximum concentration.
• tmax: time to maximum concentration.
• AUC0-t0-t: area under concentration-time curve, from 0 to the last blood sampling time point with measurable concentration.
• t1/2: elimination half-life.
Phase III - Non-inferiority:
1. Secondary efficacy endpoints
a. Number, appearance, size, location and histological classification of neoplastic and inflammatory colorectal lesions detected.
b. Adenoma detection rate, defined as the percentage of patients with at least one adenoma detected.
c. Caecal intubation rate, defined as the percentage of patients with appendiceal orifice visible to the endoscopist.
d. Ottawa Scale for bowel cleansing evaluation before washing and air insufflation for luminal distension. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase II - Dose finding:
1. During colonscopy at Visit 4
2. a. during colonoscopy after standard washing and air insufflation for luminal distension
b. from the beginning of study drug self-administration
c. 4 hours and 8 hours after completion of study drug self-administration
d. at Visit 2 and Visit 4 before colonoscopy
3. After completion of bowel preparation and before colonoscopy
Phase II - Pharmacokinetic sub-study: At Visit 2 and Visit 4.
Phase III - Non-inferiority:
1. a. during the colonoscopy at Visit 4
b. during the colonoscopy at Visit 4
c. during the colonoscopy at Visit 4
d. at Visit 4 after standard washing and air insufflation for luminal distension |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| 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) | Yes |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Same IMP Test, diffrent dose |
|
| 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
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 37 |
| 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 |
| France |
| Germany |
| Italy |
| Russian Federation |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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