Elective Colonoscopy
Conditions
Keywords
Colonoscopy preparation, Bowel cleansing, Gas, Mannitol
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 .
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: 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
Interventions
DRUGPhase 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
DRUGPhase 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
DRUGPhase 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
DRUGPhase 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
DRUGPhase 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.
Sponsors
NTC srl
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Masking description
Endoscopist-blinded
Intervention model description
A randomized, parallel-group study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase II - Dose Finding: Proportion of Patients With Adequate Bowel Cleansing | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed | 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). |
| Phase III - Non-inferiority: Proportion of Patients With Adequate Bowel Cleansing | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration | 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 | descriptive statistics (mean) of peak plasma concentration (Cmax) as pharmacokinetic parameter. |
| Phase III - Non-inferiority: Adenoma Detection Rate | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed | The percentage of patients with at least one lesion detected. |
| Phase III - Non-inferiority: Ottawa Bowel Preparation Scale (OBPS) | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed | 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). |
| Phase III - Non-inferiority: Caecal Intubation Rate | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed | The percentage of patients with appendiceal orifice visible to the endoscopist. |
| Phase III - Non-inferiority: Bowel Cleansing Impact Review (BOCLIR) (Italian Sites Only) | 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 | 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. |
| Phase III - Non-inferiority: Adherence to Bowel Preparation With Mannitol and With Moviprep®. | 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 | Proportion of patients that completely taken, partially taken or not taken assigned mannitol dose |
| Phase III - Non-inferiority: Ease of Use | 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 | 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 | 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 | Proportion of patient who confirmed that they would like to reuse the preparation for other colonoscopies. |
| Phase III - Non-inferiority: Treatment Acceptability | 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 | Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good). |
| Phase II - Dose Finding: Caecal Intubation Rate | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed | 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. |
| Phase II - Dose Finding: Adherence to Bowel Preparation | 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 | Proportion of patient that completely taken assigned mannitol dose. |
| Phase II - Dose Finding: Ease of Use | 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) | Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (very difficult) to 10 (very easy). |
| Phase II - Dose Finding: Willingness to Reuse the Preparation | 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 | Proportion of patient who confirmed that they would like to reuse the preparation for other colonoscopies. |
| Phase II - Dose Finding: Treatment Acceptability | 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 | Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good). |
| Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration | 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 | Descriptive statistics (Median) of time to maximum concentration (tmax) as pharmacokinetic parameter. |
| Phase II - Pharmacokinetic Parameter: Area Under the Curve | 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 | 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 | 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 | Descriptive statistics (Mean) of elimination half life (t1/2), as pharmacokinetic parameter. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Vital Signs During Colonoscopy | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed | Proportion of patients with change of vital signs during colonoscopy considered clinically significant by the Investigator (heart rate and pulse oximetry). |
| Phase III - Dose Finding:Patients in Safe Condition Related to Potentially Critical Concentration of Gases (H2/CH4) | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed | Proportion of patients in safe condition for intestinal gases defined as concentration of potentially critical concentration of gases (H2\>4% and CH4 \>5%) |
| 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 (during the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed) | Incidence of adverse events occuring starting from enrollment |
| Phase III - Non-inferiority: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 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. |
| Phase III - Non-inferiority: Proportion of Patients With Change of Vital Signs From Baseline and During Colonoscopy | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed, 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. |
| 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 (during the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed) | Incidence of adverse events occuring starting from enrollment |
| Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 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. |
| Phase II - Dose Finding: Patients in Safe Condition Related to Potentially Critical Concentrations of Gases (H2/CH4) | During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed after standard washing and air insufflation for luminal distension | Proportion of patients in safe condition for intestinal gases defined as concentration of potentially critical concentrations of gases (H2\>4% and CH4 \>5%) |
Countries
France, Germany, Italy, Russia
Participant flow
Recruitment details
Study period: * Phase II study initiation date: 22 June 2020 * Phase II LPLV: 12 November 2020 * Phase III study initiation date: 2 March 2021 * Phase III LPLV: 16 July 2021 * Phase II: 6 centres in Italy, 2 centres in Germany and 1 centre in France * Phase III: 32 centres located in Italy, Germany, France, and Russia
Pre-assignment details
Phase II Planned sample size n.150; screened patients n.199; screen failures n.16; randomized patients n.183; completed patients: 179 Phase III Planned sample size n.696; screened patients n. 841; withdrawal patients n. 7; screen failures n. 131; randomized patients n.703; completed patients: 683
Participants by arm
| Arm | Count |
|---|---|
| Phase II: NTC015 Low Dose Mannitol 50 g administered as single dose | 66 |
| Phase II: NTC015 Medium Dose Mannitol 100 g administered as single dose | 57 |
| Phase II: NTC015 High Dose Mannitol 150 g administered as single dose | 60 |
| Phase III: NTC015 Selected Dose Mannitol 100 g selected from phase II, single dose | 352 |
| Phase III: 2L PEG ASC (Moviprep®) 2 L polyethylene glycol plus ascorbate solution, split dose | 351 |
| Total | 886 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Other | 1 | 0 | 2 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 9 | 6 |
Baseline characteristics
| Characteristic | Phase II: NTC015 Low Dose | Phase II: NTC015 Medium Dose | Phase II: NTC015 High Dose | Phase III: NTC015 Selected Dose | Phase III: 2L PEG ASC (Moviprep®) | Total |
|---|---|---|---|---|---|---|
| Age, Customized Age at study entry | 57.55 years STANDARD_DEVIATION 11.15 | 54.4 years STANDARD_DEVIATION 11.19 | 53.8 years STANDARD_DEVIATION 13.78 | 54.8 years STANDARD_DEVIATION 12.65 | 54.6 years STANDARD_DEVIATION 12.71 | 54.7 years STANDARD_DEVIATION 12.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 3 Participants | 4 Participants | 4 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants | 54 Participants | 56 Participants | 343 Participants | 344 Participants | 860 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 3 Participants | 13 Participants |
| Female reproductive status Childbearing potential | 8 Participants | 6 Participants | 15 Participants | 103 Participants | 100 Participants | 232 Participants |
| Female reproductive status Menopause | 20 Participants | 23 Participants | 21 Participants | 106 Participants | 87 Participants | 257 Participants |
| Female reproductive status Other | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Female reproductive status Sterile | 2 Participants | 3 Participants | 0 Participants | 9 Participants | 8 Participants | 22 Participants |
| Sex: Female, Male Female | 30 Participants | 32 Participants | 36 Participants | 219 Participants | 196 Participants | 513 Participants |
| Sex: Female, Male Male | 36 Participants | 25 Participants | 24 Participants | 133 Participants | 155 Participants | 373 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 57 | 0 / 57 | 0 / 343 | 0 / 347 |
| other Total, other adverse events | 3 / 65 | 8 / 57 | 17 / 57 | 25 / 343 | 9 / 347 |
| serious Total, serious adverse events | 0 / 65 | 0 / 57 | 1 / 57 | 3 / 343 | 0 / 347 |
Outcome results
Primary
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
Population: Percentages were computed on patients belonging to the PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Proportion of Patients With Adequate Bowel Cleansing | 0.75 Proportion of patients |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Proportion of Patients With Adequate Bowel Cleansing | 0.94 Proportion of patients |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Proportion of Patients With Adequate Bowel Cleansing | 0.94 Proportion of patients |
Primary
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
Population: Percentages were computed on patients belonging to the PP Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Proportion of Patients With Adequate Bowel Cleansing | 0.91 Proportion of patients |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Proportion of Patients With Adequate Bowel Cleansing | 0.95 Proportion of patients |
Secondary
Phase II - Dose Finding: Adherence to Bowel Preparation
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
Population: Percentages were computed on patients belonging to the PP population. Overall Number of Participants Analyzed referred to patient that completely taken assigned mannitol dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Adherence to Bowel Preparation | 60 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Adherence to Bowel Preparation | 54 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Adherence to Bowel Preparation | 49 Participants |
Secondary
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
Population: Percentages were computed on patients belonging to the PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Caecal Intubation Rate | 0.92 Proportion of patients |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Caecal Intubation Rate | 1 Proportion of patients |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Caecal Intubation Rate | 1 Proportion of patients |
Secondary
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)
Population: Percentages were computed on patients belonging to the PP population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Ease of Use | 9.6 Score | Standard Deviation 0.7 |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Ease of Use | 9.3 Score | Standard Deviation 1.09 |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Ease of Use | 9.1 Score | Standard Deviation 1.36 |
Secondary
Phase II - Dose Finding: Treatment Acceptability
Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good).
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
Population: Percentages were computed on patients belonging to the PP population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Treatment Acceptability | 9.2 score on a scale | Standard Deviation 1.01 |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Treatment Acceptability | 8.3 score on a scale | Standard Deviation 1.49 |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Treatment Acceptability | 8.0 score on a scale | Standard Deviation 1.94 |
Secondary
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.
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
Population: Percentages were computed on patients belonging to the PP population.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Willingness to Reuse the Preparation | No | 0 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Willingness to Reuse the Preparation | Yes | 60 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Willingness to Reuse the Preparation | No | 3 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Willingness to Reuse the Preparation | Yes | 51 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Willingness to Reuse the Preparation | No | 3 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Willingness to Reuse the Preparation | Yes | 46 Participants |
Secondary
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
Population: Percentages were computed on patients belonging to the Full Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Adenoma Detection Rate | Adenoma detection rate - Yes | 98 Number of patients |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Adenoma Detection Rate | Adenoma detection rate - No | 235 Number of patients |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Adenoma Detection Rate | Adenoma detection rate - Yes | 103 Number of patients |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Adenoma Detection Rate | Adenoma detection rate - No | 244 Number of patients |
Secondary
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
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
Population: Percentages were computed on patients belonging to the Safety set who have been administered questionnaire on adherence and acceptability.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Adherence to Bowel Preparation With Mannitol and With Moviprep®. | Completely taken (fully drinked) | 341 Number of patients |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Adherence to Bowel Preparation With Mannitol and With Moviprep®. | Partially taken | 0 Number of patients |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Adherence to Bowel Preparation With Mannitol and With Moviprep®. | Completely taken (fully drinked) | 341 Number of patients |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Adherence to Bowel Preparation With Mannitol and With Moviprep®. | Partially taken | 6 Number of patients |
Secondary
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
Population: Percentages were computed on patients belonging to Italian centers in the Safety set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Bowel Cleansing Impact Review (BOCLIR) (Italian Sites Only) | 23.5 score on a scale | Standard Deviation 13.48 |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Bowel Cleansing Impact Review (BOCLIR) (Italian Sites Only) | 31.5 score on a scale | Standard Deviation 16.26 |
Secondary
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
Population: Percentages were computed on patients belonging to the Full Analysis Set.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Caecal Intubation Rate | Yes | 327 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Caecal Intubation Rate | No | 6 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Caecal Intubation Rate | Yes | 345 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Caecal Intubation Rate | No | 2 Participants |
Secondary
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).
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
Population: Percentages were computed on patients belonging to the Safety set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Ease of Use | 9.3 score on a scale | Standard Deviation 1.41 |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Ease of Use | 8.5 score on a scale | Standard Deviation 2 |
Secondary
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
Population: Percentages were computed on patients belonging to the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Ottawa Bowel Preparation Scale (OBPS) | 4.4 score on a scale | Standard Deviation 3.08 |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Ottawa Bowel Preparation Scale (OBPS) | 3.6 score on a scale | Standard Deviation 2.52 |
Secondary
Phase III - Non-inferiority: Treatment Acceptability
Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good).
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
Population: Percentages were computed on patients belonging to the Safety set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Treatment Acceptability | 8.3 score on a scale | Standard Deviation 1.74 |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Treatment Acceptability | 5.6 score on a scale | Standard Deviation 2.67 |
Secondary
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.
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
Population: Percentages were computed on patients belonging to the Safety set who have been administered questionnaire on adherence and ac ceptability.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Willingness to Reuse the Preparation | Yes | 331 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Willingness to Reuse the Preparation | No | 10 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Willingness to Reuse the Preparation | Yes | 272 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Willingness to Reuse the Preparation | No | 75 Participants |
Secondary
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.
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
Population: Percentages were computed on patients belonging to the PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Pharmacokinetic Parameter: Area Under the Curve | 2.2313 mg/mL*hours | Standard Deviation 0.52086 |
| Phase II: NTC015 Medium Dose | Phase II - Pharmacokinetic Parameter: Area Under the Curve | 4.1591 mg/mL*hours | Standard Deviation 1.3482 |
| Phase II: NTC015 High Dose | Phase II - Pharmacokinetic Parameter: Area Under the Curve | 5.8476 mg/mL*hours | Standard Deviation 2.36432 |
Secondary
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
Population: Percentages were computed on patients belonging to the PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration | 0.6304 Mannitol plasma concentrations (mg/mL) | Standard Deviation 0.14536 |
| Phase II: NTC015 Medium Dose | Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration | 1.0236 Mannitol plasma concentrations (mg/mL) | Standard Deviation 0.27877 |
| Phase II: NTC015 High Dose | Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration | 1.3729 Mannitol plasma concentrations (mg/mL) | Standard Deviation 0.38338 |
Secondary
Phase II - Pharmacokinetic Parameter: Terminal Elimination Half Life
Descriptive statistics (Mean) of elimination half life (t1/2), 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
Population: Percentages were computed on patients belonging to the PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Pharmacokinetic Parameter: Terminal Elimination Half Life | 2.5838 Hours | Standard Deviation 0.83985 |
| Phase II: NTC015 Medium Dose | Phase II - Pharmacokinetic Parameter: Terminal Elimination Half Life | 2.4186 Hours | Standard Deviation 0.57883 |
| Phase II: NTC015 High Dose | Phase II - Pharmacokinetic Parameter: Terminal Elimination Half Life | 2.6782 Hours | Standard Deviation 0.48912 |
Secondary
Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration
Descriptive statistics (Median) of time to maximum concentration (tmax) 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
Population: Percentages were computed on patients belonging to the PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration | 1.1173 Hours | Standard Deviation 0.3611 |
| Phase II: NTC015 Medium Dose | Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration | 1.3636 Hours | Standard Deviation 0.52259 |
| Phase II: NTC015 High Dose | Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration | 1.4488 Hours | Standard Deviation 0.80422 |
Other Pre-specified
Phase II - Dose Finding: Incidence of Adverse Events
Incidence of adverse events occuring starting from enrollment
Time frame: Visit 2 (≤ 7 days before Visit 4), Visit 3 (≤ 7 days before Visit 4) and Visit 4 (during the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed)
Population: Percentages were computed on patients belonging to the Safety set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE leading to colonoscopy interruption | 0 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE | 7 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE related to colonoscopy | 0 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one AESI | 1 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE related to study drug | 2 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE related to colonoscopy | 1 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one fatal TESAE | 0 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE | 0 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE leading to study drug withdrawal | 0 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE related to study drug | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE leading to study drug withdrawal | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE leading to colonoscopy interruption | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE related to study drug | 6 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one fatal TESAE | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one AESI | 7 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE related to study drug | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE | 11 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE related to colonoscopy | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE related to colonoscopy | 1 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one AESI | 11 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE | 19 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE related to study drug | 12 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE related to study drug | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE related to colonoscopy | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE related to colonoscopy | 2 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TEAE leading to study drug withdrawal | 1 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE leading to colonoscopy interruption | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one fatal TESAE | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Incidence of Adverse Events | Patients with at least one TESAE | 1 Participants |
Other Pre-specified
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%)
Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed after standard washing and air insufflation for luminal distension
Population: Percentages were computed on patients belonging to the PP population evaluable for potentially dangerous levels of H2 and CH4
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Patients in Safe Condition Related to Potentially Critical Concentrations of Gases (H2/CH4) | Proportion of patients with potentially dangerous levels of H2 | 0 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Patients in Safe Condition Related to Potentially Critical Concentrations of Gases (H2/CH4) | Proportion of patients with potentially dangerous levels of CH4 | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Patients in Safe Condition Related to Potentially Critical Concentrations of Gases (H2/CH4) | Proportion of patients with potentially dangerous levels of H2 | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Patients in Safe Condition Related to Potentially Critical Concentrations of Gases (H2/CH4) | Proportion of patients with potentially dangerous levels of CH4 | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Patients in Safe Condition Related to Potentially Critical Concentrations of Gases (H2/CH4) | Proportion of patients with potentially dangerous levels of H2 | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Patients in Safe Condition Related to Potentially Critical Concentrations of Gases (H2/CH4) | Proportion of patients with potentially dangerous levels of CH4 | 0 Participants |
Other Pre-specified
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.
Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours and 8 hours after completion of study drug self administration
Population: Percentages were computed on patients belonging to the Safety set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (hematological parameters) | 0 Participants |
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (chemical parameters) | 1 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (hematological parameters) | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (chemical parameters) | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (hematological parameters) | 2 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (chemical parameters) | 2 Participants |
Other Pre-specified
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).
Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase II: NTC015 Low Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Vital Signs During Colonoscopy | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Vital Signs During Colonoscopy | 0 Participants |
| Phase II: NTC015 High Dose | Phase II - Dose Finding: Proportion of Patients With Clinically Significant Change of Vital Signs During Colonoscopy | 0 Participants |
Other Pre-specified
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%)
Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed
Population: Percentages were computed on patients belonging to the safety set evaluable for potentially dangerous levels of H2 and CH4. Some patients were excluded from the analysis because their gas concentrations were measured through a device with malfunction issues
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Dose Finding:Patients in Safe Condition Related to Potentially Critical Concentration of Gases (H2/CH4) | Proportion of patients with potentually dangerous levels H2 | 0 Participants |
| Phase II: NTC015 Low Dose | Phase III - Dose Finding:Patients in Safe Condition Related to Potentially Critical Concentration of Gases (H2/CH4) | Proportion of patients with potentually dangerous levels CH4 | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Dose Finding:Patients in Safe Condition Related to Potentially Critical Concentration of Gases (H2/CH4) | Proportion of patients with potentually dangerous levels H2 | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Dose Finding:Patients in Safe Condition Related to Potentially Critical Concentration of Gases (H2/CH4) | Proportion of patients with potentually dangerous levels CH4 | 0 Participants |
Other Pre-specified
Phase III - Non-inferiority: Incidence of Adverse Events
Incidence of adverse events occuring starting from enrollment
Time frame: Visit 2 (≤ 7 days before Visit 4), Visit 3 (≤ 7 days before Visit 4) and Visit 4 (during the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed)
Population: Percentages were computed on patients belonging to the Safety set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE | 52 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TESAE | 3 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE related to study drug | 32 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TESAE related to study drug | 3 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE related to study drug leading to study drug withdrawal | 1 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TESAE related to study drug leading to study drug withdrawal | 0 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE related to colonoscopy | 5 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TESAE related to colonoscopy | 0 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE leading to study drug withdrawal | 1 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE leading to colonoscopy interruption | 1 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one fatal TESAE | 0 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one treatment-emergent AESI | 27 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one fatal TESAE | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE | 36 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE related to colonoscopy | 2 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TESAE | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE leading to colonoscopy interruption | 1 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE related to study drug | 14 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TESAE related to colonoscopy | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TESAE related to study drug | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one treatment-emergent AESI | 9 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE related to study drug leading to study drug withdrawal | 1 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TEAE leading to study drug withdrawal | 1 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Incidence of Adverse Events | Patients with at least one TESAE related to study drug leading to study drug withdrawal | 0 Participants |
Other Pre-specified
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.
Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed, prior to colonoscopy
Population: Percentages were computed on patients belonging to the Safety set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Proportion of Patients With Change of Vital Signs From Baseline and During Colonoscopy | 2 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Proportion of Patients With Change of Vital Signs From Baseline and During Colonoscopy | 1 Participants |
Other Pre-specified
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.
Time frame: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours and 8 hours after completion of study drug self-administration
Population: Percentages were computed on patients belonging to the Safety set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (Hematology) | 2 Participants |
| Phase II: NTC015 Low Dose | Phase III - Non-inferiority: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (Clinical chemistry) | 12 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (Hematology) | 0 Participants |
| Phase II: NTC015 Medium Dose | Phase III - Non-inferiority: Proportion of Patients With Clinically Significant Change of Haematological and Chemical Parameters From Baseline | Patients with at least one clinically significant abnormality (Clinical chemistry) | 5 Participants |