Subjects scheduled for elective colonoscopy to be prepared and performed according to ESGE (European Society of Gastrointestinal Endoscopy - ESGE) guidelines. MedDRA version: 21.0 Level: PT Classification code 10010007 Term: Colonoscopy System Organ Class: 10022891 - Investigations
Conditions
Interventions
Product Name: Pearlitol® PF
Product Code: Mannitol solution
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: MANNITOL
Current Sponsor code: Pearlitol® PF
Other descriptive name: Mann
Sponsors
NTC s.r.l.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability of patient to consent and provide signed 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 423 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 423
Exclusion criteria
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. Severe acute and chronically active Inflammatory Bowel Disease; patients in clinical remission (Crohn's Disease Activity Index - CDAI < 150 for Crohn Disease and Partial Mayo Score = 2 for Ulcerative Colitis) are allowed. 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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®.;Secondary Objective: NA;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.;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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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% Vol >100% of Lower Explosion Level (LEL), which is equal to 5% Vol, 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 during colonoscopy considered clinically significant by the Investigator of vital signs (heart rate, and pulse oximetry). Of note, a clinically significant change of a given parameter is defined as a change that causes an additional control or a medical intervention. 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 | — |
Countries
France, Germany, Italy, Russian Federation
Contacts
Public ContactDipartimento Medico
OPIS s.r.l.
Outcome results
None listed