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

NTC srl886 enrolled

Overview

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 Start and Study Completion dates relative to the Phase II/III are reported here: Phase II (Patients n. 183) * Date of first enrolment: 18 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

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

SINGLE

Enrollment

886

Conditions

Elective Colonoscopy

Interventions

Phase II: NTC015 low doseDRUG

Participants should self administer the preparation within 30 minutes and drink clear liquid according to local practice at the centre to prevent dehydration

Phase II: NTC015 medium doseDRUG

Participants should self administer the preparation within 30 minutes and drink clear liquid according to local practice at the centre to prevent dehydration

Phase II: NTC015 high doseDRUG

Participants should self administer the preparation within 60 minutes and drink clear liquid according to local practice at the centre to prevent dehydration

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (35)

Outcomes

Primary Outcomes

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 ≥ 2 during colonoscopy after standard washing and air insufflation for luminal distension. The mannitol dose to be used in phase III was singled out on an algorithm that calculated a total score for each dose starting from the scores assigned to the three main criteria through a ranking system and proportionally to the importance given to each main criterion: A - rate of adequate bowel cleansing (most important - primary endpoint), B - rate of patients in safe conditions and C - clinical judgement score (least important - partially based on subjective assessments).

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed

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.

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed, at least 4 hours after end of intake, following product instruction as per protocol

Secondary Outcomes

Phase II - Dose Finding: Caecal Intubation Rate

The percentage of patients with appendiceal orifice visible to the endoscopist. Evaluation will be performed during conduction of colonoscopy run on visit 4. Timing for treatment administration was described in the protocol and change among arms.

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed

Phase II - Dose Finding: Adherence to Bowel Preparation

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Participants should self administer the preparation within 30 minutes and drink clear liquid according to local practice at the centre to prevent dehydration

Phase III: Polyethylene glycol plus ascorbate solution (2L PEG ASC)DRUG

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.

Centre Hospitalier Henri Duffaut

Avignon, France

Hospices civils de Lyon

Lyon, France

Hôpital Edouard Herriot

Lyon, France

Centre Hospitalier Universitaire de Montpellier

Montpellier, France

Klinikum der Stadt Ludwigshafen

Ludwigshafen, Germany

Praxis für Gastroenterologie und Fachärztliche Innere Medizin, Im Haus der Gesundheit

Ludwigshafen am Rhein, Germany

Katholisches Klinikum Mainz

Mainz, Germany

Klinikum Worms Medizinische Klinik II

Worms, Germany

IRCCS "Saverio De Bellis"

Castellana Grotte, BA, Italy

Fondazione Poliambulanza - Istituto Ospedaliero

Brescia, BR, Italy

...and 25 more locations

Proportion of patient that completely taken assigned mannitol dose.

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed, 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).

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours after the end of study drug self-administration, before colonoscopy (please refer to protocol)

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.

Phase II - Dose Finding: Treatment Acceptability

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

Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration

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

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. Before mannitol self-administration 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.

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.

Phase II - Pharmacokinetic Parameter: Terminal Elimination Half Life

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

Phase III - Non-inferiority: Adenoma Detection Rate

The percentage of patients with at least one lesion detected.

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed

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).

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed

Phase III - Non-inferiority: Caecal Intubation Rate

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

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed

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.

Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 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

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).

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.

Phase III - Non-inferiority: Treatment Acceptability

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