Efficacy and Safety of mAnnitol in Bowel Preparation During Elective Colonoscopy and Comparison With Moviprep® (SATISFACTION)

Efficacy and Safety of mAnniTol in Bowel Preparation: Assessment of Adequacy and Presence of Intestinal levelS of Hydrogen and Methane During Elective Colonoscopy aFter mAnnitol or Standard Split 2-liter Polyethylene Glycol Solution Plus asCorbaTe - a Phase II/III, International, Multicentre, Randomized, Parallel-group, endoscOpist-bliNded, Dose-finding/Non-inferiority Study - SATISFACTION

The purpose of this dose finding/comparative efficacy study is to first single out the most appropriate dose of mannitol for bowel preparation (phase II) and, subsequently, demonstrate the non-inferiority of the efficacy of single dose mannitol vs standard split 2L PEG ASC (Moviprep®) (phase III) in bowel preparation for colonoscopy .

Study Overview

• Status: Completed
• Conditions: Elective Colonoscopy
• Intervention / Treatment: Drug: Phase II: NTC015 low dose; Drug: Phase II: NTC015 medium dose; Drug: Phase II: NTC015 high dose; Drug: Phase III: NTC015 selected dose; Drug: Phase III: Polyethylene glycol plus ascorbate solution (2L PEG ASC)

Detailed Description

Study Start and Study Completion dates relative to the Phase II/III are reported here:

Phase II (Patients n. 183)

• Date of first enrolment: 22 June 2020
• Date LPLV: 12 November 2020

Phase III (Patients n. 703)

• Date of first enrolment: 2 March 2021
• Date LPLV: 16 July 2021

Date on which the study was entered in the EudraCT database: 13 October 2020

• Study Type: Interventional
• Enrollment (Actual): 886
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Avignon, France
    • Centre Hospitalier Henri Duffaut
  • Lyon, France
    • Hospices Civils de Lyon
  • Lyon, France
    • Hôpital Edouard Herriot
  • Montpellier, France
    • Centre Hospitalier Universitaire de Montpellier
• Germany
  • Ludwigshafen, Germany
    • Klinikum der Stadt Ludwigshafen
  • Ludwigshafen am Rhein, Germany
    • Praxis für Gastroenterologie und Fachärztliche Innere Medizin, Im Haus der Gesundheit
  • Mainz, Germany
    • Katholisches Klinikum Mainz
  • Worms, Germany
    • Klinikum Worms Medizinische Klinik II
• Italy
  • Novara, Italy, 28100
    • Azienda Ospedaliero-Universitaria Maggiore della Carità
  • Varese, Italy, 21100
    • ASST Sette Laghi - Ospedale di Circolo e Fondazione Macchi
  • BA
    • Castellana Grotte, BA, Italy, 70013
      • IRCCS "Saverio de Bellis"
  • BR
    • Brescia, BR, Italy, 25124
      • Fondazione Poliambulanza - Istituto Ospedaliero
  • CI
    • Iglesias, CI, Italy
      • ASSL Carbonia - Presidio Ospedaliero CTO di Iglesias
  • CO
    • Como, CO, Italy
      • Ospedale Valduce
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • Fondazione Casa Sollievo della Sofferenza
  • MI
    • Garbagnate Milanese, MI, Italy, 20024
      • ASST Rhodense - Presidi di Rho e Garbagnate
    • Milano, MI, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda
    • Milano, MI, Italy, 20122
      • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
    • Milano, MI, Italy
      • IRCCS Ospedale San Raffaele
    • Milano, MI, Italy
      • Istituto Europeo Di Oncologia
    • San Donato Milanese, MI, Italy, 20097
      • IRCCS Policlinico San Donato
  • MO
    • Carpi, MO, Italy, 41012
      • Azienda USL di Modena - Ospedale Ramazzini di Carpi
  • PI
    • Pisa, PI, Italy, 56124
      • Azienda Ospedaliero Universitaria Pisana- Ospedale Cisanello
  • PN
    • Aviano, PN, Italy, 33081
      • Centro di Riferimento Oncologico IRCCS
  • RO
    • Roma, RO, Italy, 00168
      • Policlinico Universitario A. Gemelli
  • TN
    • Trento, TN, Italy, 38100
      • Presidio Ospedaliero Santa Chiara
  • VR
    • Negrar, VR, Italy, 37024
      • Ospedale Sacro Cuore
• Russian Federation
  • Irkutsk, Russian Federation
    • Irkutsk State Medical Academy of Postgraduate Education
  • Moscow, Russian Federation
    • Clinical Hospital of Russian Railways N.A. Semashko
  • Moscow, Russian Federation
    • Moscow Clinical Research and Practical Center of the Department of Health
  • Moscow, Russian Federation
    • State Central Clinical Hospital A. N. Ryzhykh
  • Rostov, Russian Federation
    • Railway Clinical Hospital
  • Samara, Russian Federation
    • Private educational organization of higher education "Medical University "Reaviz"
  • Yaroslavl, Russian Federation
    • Medical Center of Diagnostics and Prevention
  • Yaroslavl, Russian Federation
    • Regional Oncological Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase II: NTC015 low dose (Mannitol 50 g); One day single dose preparation same day of colonoscopy	Drug: Phase II: NTC015 low dose; Participants should self administer the preparation within 30 minutes and drink clear liquid according to local practice at the centre to prevent dehydration
Experimental: Phase II: NTC015 medium dose (Mannitol 100 g); One day single dose preparation same day of colonoscopy	Drug: Phase II: NTC015 medium dose; Participants should self administer the preparation within 30 minutes and drink clear liquid according to local practice at the centre to prevent dehydration
Experimental: Phase II: NTC015 high dose (Mannitol 150 g); One day single dose preparation same day of colonoscopy	Drug: Phase II: NTC015 high dose; Participants should self administer the preparation within 60 minutes and drink clear liquid according to local practice at the centre to prevent dehydration
Experimental: Phase III: NTC015 selected dose; One day single dose preparation same day of colonoscopy	Drug: Phase III: NTC015 selected dose; Participants should self administer the preparation within 30 minutes and drink clear liquid according to local practice at the centre to prevent dehydration
Active Comparator: Phase III: Polyethylene glycol plus ascorbate solution (2L PEG ASC) (Moviprep®); Two litres of Moviprep® taken according to split-dose regimen (to commence in the evening before colonoscopy)	Drug: Phase III: Polyethylene glycol plus ascorbate solution (2L PEG ASC); The instructions for product administration are followed according to the Summary of Product Characteristics. One treatment consists of two litres of Moviprep® taken according to split-dose regimen. The first litre of Moviprep® is prepared by dissolving one sachet A and one sachet B together in water to make one litre of solution. The reconstituted solution must be drunk over a period of one to two hours the evening before colonoscopy. About half a litre of clear liquid should be drunk in the next hour to prevent dehydration according to local practice at the centre. This process should be repeated with a second litre of Moviprep® prepared by dissolving one sachet A and one sachet B together in water to make one litre of solution in the early morning of the day of the procedure.; Other Names: Moviprep®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II - Dose finding: Proportion of patients with adequate bowel cleansing	Proportion of patients with adequate bowel cleansing, defined as 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 during colonoscopy after standard washing and air insufflation for luminal distension.	During colonoscopy (Visit 4)
Phase III - Non-inferiority: Proportion of patients with adequate bowel cleansing	Proportion of patients with adequate bowel cleansing, defined as 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 during colonoscopy after standard washing and air insufflation for luminal distension.	During colonoscopy (Visit 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II - Dose finding: Caecal intubation rate	The percentage of patients with appendiceal orifice visible to the endoscopist.	During colonoscopy at Visit 4
Phase II - Dose finding: Adherence to bowel preparation	Proportion of patient that completely taken, partially taken or not taken assigned mannitol dose.	During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
Phase II - Dose finding: ease of use	Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (very difficult) to 10 (very easy).	During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
Phase II - Dose finding: Willingness to reuse the preparation	Proportion of patient who confirmed that they would like to reuse the preparation for other colonoscopies.	During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
Phase II - Dose finding: Treatment acceptability	Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good).	During visit 4 (day of colonoscopy), 4 hours after the end of study drug self-administration, before colonoscopy
Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration	descriptive statistics (mean) of peak plasma concentration (Cmax) as pharmacokinetic parameter.	During vist 4 (day of colonoscopy), before mannitol self-administration (T0 - baseline),1 hour (T1), 2 hours (T2), 4 hours (T4) and 8 hours (T8) after completion of mannitol self-administration
Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration	Descriptive statistics (Median) of time to maximum concentration (tmax) as pharmacokinetic parameter.	During vist 4 (day of colonoscopy), before mannitol self-administration (T0 - baseline),1 hour (T1), 2 hours (T2), 4 hours (T4) and 8 hours (T8) after completion of mannitol self-administration
Phase II - Pharmacokinetic Parameter: Area Under the Curve	Descriptive statistics (Mean) of area under the curve from t0 to the last blood sampling time point (AUC 0-t8), as pharmacokinetic parameter.	During vist 4 (day of colonoscopy), before mannitol self-administration (T0 - baseline),1 hour (T1), 2 hours (T2), 4 hours (T4) and 8 hours (T8) after completion of mannitol self-administration
Phase II - Pharmacokinetic Parameter: Elimination Half Life	Descriptive statistics (Mean) of elimination half life (t1/2), as pharmacokinetic parameter.	During vist 4 (day of colonoscopy), before mannitol self-administration (T0 - baseline),1 hour (T1), 2 hours (T2), 4 hours (T4) and 8 hours (T8) after completion of mannitol self-administration
Phase III - Non-inferiority: Adenoma detection rate	The percentage of patients with at least one lesion detected.	During the colonoscopy at Visit 4
Phase III - Non-inferiority: Ottawa Bowel Preparation Scale (OBPS)	Ottawa scale is used to measure the quality of the preparation in three different parts of the colon before washing and insufflation. descriptive statistics (Mean) of the total score (from 0 excellent to 14 inadequate).	During the colonoscopy at Visit 4
Phase III - Non-inferiority: Caecal intubation rate	The percentage of patients with appendiceal orifice visible to the endoscopist.	During the colonoscopy at Visit 4
Phase III - Non-inferiority: Bowel Cleansing Impact Review (BOCLIR) (Italian sites only)	The BOCLIR is a questionnaire filled in by patients to measure the acceptability and tolerability of bowel cleansers consisting of three unidimensional scales (satisfaction, symptoms and activity limitations) with good psychometric and scaling properties. Item responses are summed to provide a score for each scale and a total score. The satisfaction scale contains eight items and the score ranges from 0 (highly satisfied) to 32 (highly dissatisfied). The symptoms scale includes 14 items and the score ranges from 0 (no symptoms) to 42 (severe symptoms). The activity limitations scale is made up of 12 items and the score ranges from 0 (no effect on activities) to 36 (activities greatly affected). The total score is the sum of the three scales and ranges from 0 to 110. Patients who report a worse experience in terms of the three factors score higher on the BOCLIR scale.	Visit 4 after the end of study drug self-administration, before colonoscopy
Phase III - Non-inferiority: Adherence to bowel preparation with mannitol and with Moviprep®.	Proportion of patients that completely taken, partially taken or not taken assigned mannitol dose	During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
Phase III - Non-inferiority: ease of use	Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (very difficult) to 10 (very easy).	During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
Phase III - Non-inferiority: Willingness to reuse the preparation	Proportion of patient who confirmed that they would like to reuse the preparation for other colonoscopies.	During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
Phase III - Non-inferiority: Treatment acceptability	Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good).	During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II - Dose finding: Patients in safe condition related to potentially critical concentrations of gases (H2/CH4)	Proportion of patients in safe condition for intestinal gases defined as concentration of potentially critical concentrations of gases (H2>4% and CH4 >5%)	During colonoscopy after standard washing and air insufflation for luminal distension at Visit 4
Phase II - Dose finding: Incidence of adverse events	Incidence of adverse events from the enrollment	Visit 2 (≤ 7 days before Visit 4), Visit 3 (≤ 7 days before Visit 4) and Visit 4 (day of colonoscopy)
Phase II - Dose finding: Proportion of patients with clinically significant change of haematological and chemical parameters from baseline	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) 4 hours and 8 hours after completion of study drug self-administration.	During visit 4 (day of colonoscopy), 4 hours and 8 hours after completion of study drug self administration
Phase II - Dose finding: Proportion of patients with clinically significant change of vital signs during colonoscopy	Proportion of patients with change of vital signs during colonoscopy considered clinically significant by the Investigator (heart rate and pulse oximetry).	During the colonoscopy at Visit 4
Phase III - Dose finding:Patients in safe condition related to potentially critical concentration of gases (H2/CH4)	Proportion of patients in safe condition for intestinal gases defined as concentration of potentially critical concentration of gases (H2>4% and CH4 >5%)	During the colonoscopy at Visit 4
Phase III - Non-inferiority: Incidence of adverse events	Incidence of adverse events from enrollment	Visit 2 (≤ 7 days before Visit 4), Visit 3 (≤ 7 days before Visit 4) and Visit 4 (day of colonoscopy)
Phase III - Non-inferiority: Proportion of patients with clinically significant change of haematological and chemical parameters from baseline	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) 4 hours and 8 hours after completion of study drug self-administration.	During visit 4 (day of colonoscopy), 4 hours and 8 hours after completion of study drug self-administration
Phase III - Non-inferiority: Proportion of patients with change of vital signs from baseline and during colonoscopy	Proportion of patients with change of vital signs from baseline considered clinically significant by the Investigator (heart rate, systolic and diastolic blood pressure), as well as clinically significant change during colonoscopy of pulse oximetry, systolic and diastolic blood pressure and heart rate.	Visit 4 prior to colonoscopy

Collaborators and Investigators

• Sponsor: NTC srl
• Investigators: Principal Investigator: Gianpiero Manes, Dr., ASST Rhodense - Presidi di Rho e Garbagnate

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): July 16, 2021
• Study Completion (Actual): July 16, 2021

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: February 15, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Gas; Colonoscopy preparation; Bowel cleansing; Mannitol
• Other Study ID Numbers: Mannitol_03-2018; 2019-002856-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No