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

• Sponsor: NTC srl (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04759885
• Collaborator: (none)
• Enrollment: 886
• Locations: 35
• Arms: 5
• Actual Duration (Months): 12.9
• Patients Per Site: 25.3
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

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 .

Condition or Disease	Intervention/Treatment	Phase
Elective Colonoscopy	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)	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 886 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A randomized, parallel-group study.A randomized, parallel-group study.
• Masking: Single (Outcomes Assessor)
• Masking Description: Endoscopist-blinded
• Primary Purpose: Diagnostic
• Official Title: 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
• Actual Study Start Date: Jun 18, 2020
• Actual Primary Completion Date: Jul 16, 2021
• Actual Study Completion Date: Jul 16, 2021

Arms and Interventions

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®

Outcome Measures

Primary Outcome Measures

1. Phase II - Dose finding: Proportion of patients with adequate bowel cleansing [During colonoscopy (Visit 4)]

   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.

2. Phase III - Non-inferiority: Proportion of patients with adequate bowel cleansing [During colonoscopy (Visit 4)]

   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.

Secondary Outcome Measures

1. Phase II - Dose finding: Caecal intubation rate [During colonoscopy at Visit 4]

   The percentage of patients with appendiceal orifice visible to the endoscopist.

2. Phase II - Dose finding: Adherence to bowel preparation [During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy]

   Proportion of patient that completely taken, partially taken or not taken assigned mannitol dose.

3. Phase II - Dose finding: ease of use [During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy]

   Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (very difficult) to 10 (very easy).

4. Phase II - Dose finding: Willingness to reuse the preparation [During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy]

   Proportion of patient who confirmed that they would like to reuse the preparation for other colonoscopies.

5. Phase II - Dose finding: Treatment acceptability [During visit 4 (day of colonoscopy), 4 hours after the end of study drug self-administration, before colonoscopy]

   Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good).

6. Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration [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]

   descriptive statistics (mean) of peak plasma concentration (Cmax) as pharmacokinetic parameter.

7. Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration [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]

   Descriptive statistics (Median) of time to maximum concentration (tmax) as pharmacokinetic parameter.

8. Phase II - Pharmacokinetic Parameter: Area Under the Curve [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]

   Descriptive statistics (Mean) of area under the curve from t0 to the last blood sampling time point (AUC 0-t8), as pharmacokinetic parameter.

9. Phase II - Pharmacokinetic Parameter: Elimination Half Life [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]

   Descriptive statistics (Mean) of elimination half life (t1/2), as pharmacokinetic parameter.

10. Phase III - Non-inferiority: Adenoma detection rate [During the colonoscopy at Visit 4]

    The percentage of patients with at least one lesion detected.

11. Phase III - Non-inferiority: Ottawa Bowel Preparation Scale (OBPS) [During the colonoscopy at Visit 4]

    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).

12. Phase III - Non-inferiority: Caecal intubation rate [During the colonoscopy at Visit 4]

    The percentage of patients with appendiceal orifice visible to the endoscopist.

13. Phase III - Non-inferiority: Bowel Cleansing Impact Review (BOCLIR) (Italian sites only) [Visit 4 after the end of study drug self-administration, before colonoscopy]

    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.

14. Phase III - Non-inferiority: Adherence to bowel preparation with mannitol and with Moviprep®. [During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy]

    Proportion of patients that completely taken, partially taken or not taken assigned mannitol dose

15. Phase III - Non-inferiority: ease of use [During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy]

    Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (very difficult) to 10 (very easy).

16. Phase III - Non-inferiority: Willingness to reuse the preparation [During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy]

    Proportion of patient who confirmed that they would like to reuse the preparation for other colonoscopies.

17. Phase III - Non-inferiority: Treatment acceptability [During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy]

    Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good).

Other Outcome Measures

1. Phase II - Dose finding: Patients in safe condition related to potentially critical concentrations of gases (H2/CH4) [During colonoscopy after standard washing and air insufflation for luminal distension at Visit 4]

   Proportion of patients in safe condition for intestinal gases defined as concentration of potentially critical concentrations of gases (H2>4% and CH4 >5%)

2. Phase II - Dose finding: Incidence of adverse events [Visit 2 (≤ 7 days before Visit 4), Visit 3 (≤ 7 days before Visit 4) and Visit 4 (day of colonoscopy)]

   Incidence of adverse events from the enrollment

3. Phase II - Dose finding: Proportion of patients with clinically significant change of haematological and chemical parameters from baseline [During visit 4 (day of colonoscopy), 4 hours and 8 hours after completion of study drug self administration]

   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.

4. Phase II - Dose finding: Proportion of patients with clinically significant change of vital signs during colonoscopy [During the colonoscopy at Visit 4]

   Proportion of patients with change of vital signs during colonoscopy considered clinically significant by the Investigator (heart rate and pulse oximetry).

5. Phase III - Dose finding:Patients in safe condition related to potentially critical concentration of gases (H2/CH4) [During the colonoscopy at Visit 4]

   Proportion of patients in safe condition for intestinal gases defined as concentration of potentially critical concentration of gases (H2>4% and CH4 >5%)

6. Phase III - Non-inferiority: Incidence of adverse events [Visit 2 (≤ 7 days before Visit 4), Visit 3 (≤ 7 days before Visit 4) and Visit 4 (day of colonoscopy)]

   Incidence of adverse events from enrollment

7. Phase III - Non-inferiority: Proportion of patients with clinically significant change of haematological and chemical parameters from baseline [During visit 4 (day of colonoscopy), 4 hours and 8 hours after completion of study drug self-administration]

   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.

8. Phase III - Non-inferiority: Proportion of patients with change of vital signs from baseline and during colonoscopy [Visit 4 prior to 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre Hospitalier Henri Duffaut	Avignon		France
2	Hospices civils de Lyon	Lyon		France
3	Hôpital Edouard Herriot	Lyon		France
4	Centre Hospitalier Universitaire de Montpellier	Montpellier		France
5	Praxis für Gastroenterologie und Fachärztliche Innere Medizin, Im Haus der Gesundheit	Ludwigshafen am Rhein		Germany
6	Klinikum der Stadt Ludwigshafen	Ludwigshafen		Germany
7	Katholisches Klinikum Mainz	Mainz		Germany
8	Klinikum Worms Medizinische Klinik II	Worms		Germany
9	IRCCS "Saverio De Bellis"	Castellana Grotte	BA	Italy	70013
10	Fondazione Poliambulanza - Istituto Ospedaliero	Brescia	BR	Italy	25124
11	ASSL Carbonia - Presidio Ospedaliero CTO di Iglesias	Iglesias	CI	Italy
12	Ospedale Valduce	Como	CO	Italy
13	Fondazione Casa Sollievo Della Sofferenza	San Giovanni Rotondo	FG	Italy	71013
14	ASST Rhodense - Presidi di Rho e Garbagnate	Garbagnate Milanese	MI	Italy	20024
15	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano	Milano	MI	Italy	20122
16	ASST Grande Ospedale Metropolitano Niguarda	Milano	MI	Italy	20162
17	IRCCS Ospedale San Raffaele	Milano	MI	Italy
18	Istituto Europeo di Oncologia	Milano	MI	Italy
19	IRCCS Policlinico San Donato	San Donato Milanese	MI	Italy	20097
20	Azienda USL di Modena - Ospedale Ramazzini di Carpi	Carpi	MO	Italy	41012
21	Azienda Ospedaliero Universitaria Pisana- Ospedale Cisanello	Pisa	PI	Italy	56124
22	Centro di Riferimento Oncologico IRCCS	Aviano	PN	Italy	33081
23	Policlinico Universitario A. Gemelli	Roma	RO	Italy	00168
24	Presidio Ospedaliero Santa Chiara	Trento	TN	Italy	38100
25	Ospedale Sacro Cuore	Negrar	VR	Italy	37024
26	Azienda Ospedaliero-Universitaria Maggiore della Carità	Novara		Italy	28100
27	ASST Sette Laghi - Ospedale di Circolo e Fondazione Macchi	Varese		Italy	21100
28	Irkutsk State Medical Academy of Postgraduate Education	Irkutsk		Russian Federation
29	Clinical Hospital of Russian Railways N.A. Semashko	Moscow		Russian Federation
30	Moscow Clinical Research and Practical Center of the Department of Health	Moscow		Russian Federation
31	State Central Clinical Hospital A. N. Ryzhykh	Moscow		Russian Federation
32	Railway Clinical Hospital	Rostov		Russian Federation
33	Private educational organization of higher education "Medical University "Reaviz"	Samara		Russian Federation
34	Medical Center of Diagnostics and Prevention	Yaroslavl		Russian Federation
35	Regional Oncological Clinical Hospital	Yaroslavl		Russian Federation

Sponsors and Collaborators

• NTC srl

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NTC srl
• ClinicalTrials.gov Identifier: NCT04759885
• Other Study ID Numbers: Mannitol_03-2018; 2019-002856-18
• First Posted: Feb 18, 2021
• Last Update Posted: Jul 12, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by NTC srl: Colonoscopy preparation; Bowel cleansing; Gas; Mannitol

Study Results

No Results Posted as of Jul 12, 2022