A phase III, international, multiCenter, randomized, paraLlel-group, Endoscopist-blinded non-inferiority study of the efficAcy, safety and patient acceptance of mannitol veRsus Plenvu® in boWel prepAration for elective colonoscopY. CLEARWAY

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ntc S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

Trial duration

3 Sep 2025 → 13 Mar 2026

Decision date (initial)

2025-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

To demonstrate the non-inferiority of mannitol vs. standard Plenvu® same-day dosing regimen in bowel cleansing for colonoscopy.

Secondary objectives 4

1. To evaluate indicators of quality in performed colonoscopies.
2. To evaluate adherence and acceptability of bowel preparation with Mannitol and with Plenvu®.
3. To assess the safety and tolerability of mannitol and Plenvu®.
4. PK sub-study: To evaluate the PK profile of 100 g Mannitol powder dissolved in 1,000 ml of water in patients with and without factors that can influence pharmacokinetic parameters (IBD, mild-to-moderate renal failure [eGFR 60-30 ml/min/1.73 m2]).

Conditions and MedDRA coding

Subjects scheduled for elective colonoscopy performed according to ESGE (European Society of Gastrointestinal Endoscopy) guidelines.

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Ability of patient to consent and provide signed written informed consent.
2. Age ≥ 18 years.
3. Males and females scheduled for elective colonoscopy performed according to ESGE guidelines.
4. Patients willing and able to complete the entire study and to comply with instructions.

Exclusion criteria 21

1. Pregnancy or breast feeding. Females of childbearing potential must have a negative pregnancy test at Visit 2 and practice highly effective methods of birth control throughout the study period, according to the CTCG “Recommendations related to contraception and pregnancy testing in clinical trials” v 1.2* (unless postmenopausal or surgically sterile, or whose sole sexual partner had a successful vasectomy).
2. Severe acute and chronically active inflammatory bowel disease; patients in clinical remission (Crohn's Disease Activity Index - CDAI < 150 for Crohn Disease (Best et al. 1976) and Partial Mayo Score ≤ 2 for Ulcerative Colitis (Schroeder et al. 1987)) are allowed.
3. History of phenylketonuria (due to presence of aspartame).
4. Severe renal failure: eGFR < 30 ml/min/1.73 m2 estimated by simplified MDRD equation.
5. Severe heart failure: New York Heart Association (NYHA) Class III-IV.
6. Severe anaemia (Hb ≤ 8 g/dl).
7. Chronic liver disease Child-Pugh class B or C.
8. Electrolyte disturbances (baseline values of Na2+, Cl-, K+ out of normal ranges).
9. Clinically significant alterations of baseline haemato-chemical parameters.
10. Recent (< 6 months) symptomatic acute ischemic heart disease.
11. History of paralysis of the gut (ileus).
12. History of disorders of gastric emptying (e.g. gastroparesis, gastric retention, etc.).
13. History of glucose-6-phosphate dehydrogenase deficiency (due to presence of ascorbate).
14. 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.
15. Use within 24 hours prior to colonoscopy of laxatives, colon motility altering drugs and/or other substances (e.g., simethicone) that could affect bowel cleansing or visibility during colonoscopy.
16. Suspected bowel obstruction or perforation.
17. Indication for partial colonoscopy.
18. Patients who received an investigational drug or therapy within 5 half-lives of the first visit.
19. Hypersensitivity to the active ingredients or to any of the excipients of the study drugs.
20. Underwater colonoscopy instead of standard gas insufflation.
21. History of toxic megacolon.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 after standard washing and air or CO2 insufflation for luminal distension.

Secondary endpoints 18

1. Adenoma detection rate, defined as the proportion of patients ≥ 45 years old without IBD undergoing colonoscopy who have at least one lesion detected.
2. Caecal intubation rate, defined as the proportion of patients undergoing colonoscopy with ileocecal junction appendiceal orifice visible to the endoscopist.
3. Proportion of patients undergoing colonoscopy who have to repeat the procedure due to inadequate intestinal cleansing to resolve, at the discretion of the endoscopist, the clinical issue underlying the request for colonoscopy.
4. Proportion of patients undergoing colonoscopy with presence of colonic bubbles assessed through the Colon Endoscopic Bubble Scale (CEBuS).
5. Number, appearance, size, location, and histological examination of neoplastic and inflammatory colorectal lesions.
6. Adherence: study drug completely taken, partially taken, not taken.
7. Ease of use: numeric rating scale (NRS) (0 = very difficult to 10 = very easy).
8. Taste: NRS (0 = terrible to 10 = very good).
9. Willingness to reuse the preparation (yes/no).
10. Satisfaction with bowel preparation compared to cleansing agent used for previous colonoscopy
11. Incidence of adverse events starting from the beginning of study drug administration.
12. Incidence of drug-related adverse events starting from the beginning of study drug self-administration
13. Proportion of patients with clinically significant change from baseline of haematological and chemical parameters 4 hours and 8 hours after completion of study drug self-administration, where clinically significant means that in the Investigator’s opinion the change needs an additional control or a medical intervention.
14. Proportion of patients with clinically significant change from baseline of heart rate, systolic and diastolic blood pressure measured from the beginning of study drug self-administration to the end of study, as well as clinically significant change of oxygen saturation during colonoscopy, where clinically significant means that in the Investigator’s opinion the change needs an additional control or a medical intervention.
15. PK sub-study: Maximum observed concentration (Cmax).
16. PK sub-study: Time to maximum observed concentration (tmax).
17. PK sub-study: Area under concentration-time curve, from 0 to the last blood sampling time point with measurable concentration (i.e., the last quantifiable timepoint) (AUC0-t0-t or AUClast).
18. PK sub-study: Terminal elimination half-life (t1/2).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ntc S.r.l.

Sponsor organisation

Ntc S.r.l.

Address

Via Luigi Razza 3

City

Milan

Postcode

20124

Country

Italy

Scientific contact point

Organisation

Ntc S.r.l.

Contact name

Dr. Alessandro Colombo

Public contact point

Organisation

Ntc S.r.l.

Contact name

Dr. Alessandro Colombo

Third parties 4

Locations

5 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 113 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications