Bowel cleansing prior to colonoscopy MedDRA version: 14.1 Level: PT Classification code 10066943 Term: Bowel preparation System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Code: TF043
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: Macrogols
CAS Number: 25322-68-3
Other descriptive name: MACROGOL 3350
Concentration unit: g gram(s)
Concentratio
Sponsors
Norgine Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) The subject’s written informed consent must be obtained prior to inclusion. (2) Subjects age 40 to 70 years. (3) Part B only: Subjects willing to undergo screening colonoscopy, where the subject: (a) is between 40 and 70 years of age and has a known personal or familial risk of colon neoplasia, or (b) is aged 55 to 70. (4) Part A only: Subjects need to be without any history of clinically significant gastrointestinal symptoms by clinical judgement and without the presence of acute abdominal discomfort or symptoms. (5) Females of child bearing potential must be surgically sterile, post-menopausal, practicing true sexual abstinence or using an acceptable form of effective contraception throughout the study from the following list: contraceptive injections, implants, oral contraceptives, intrauterine system (IUS), some intrauterine devices (IUDs), vasectomised partner or barrier method (condom or occlusive cap) with spermicidal foam/gel/film/cream/suppository. Females using oral contraceptives must also use additional contraception. Hormonal and IUD methods of contraception must be established for a period of 3 months prior to dosing and cannot be changed or altered during the study. All females must have a negative pregnancy test at screening and check-in (unless post-menopausal). (6) Willing, able and competent to complete the entire procedure and to comply with study instructions. (7) Ferrous sulphate should be stopped at least one week prior to study medication. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: (1) Part A only: Subjects undergoing screening colonoscopy. (2) Presence of current clinically significant functional gastrointestinal disorder (e.g. gastric emptying disorder, chronic constipation, irritable bowel syndrome [IBS]). (3) Regular use of laxatives or colon motility altering drugs in the last month. (4) Donation or loss of 500 mL or more of blood within 8 weeks prior to the first dose of investigational drug. (5) Any history or current presence of ileus, gastrointestinal (GI) obstruction or perforation, GI tract cancer, inflammatory bowel disease (IBD) or colonic resection. (6) Known glucose-6-phosphatase dehydrogenase deficiency. (7) Known phenylketonuria. (8) History or evidence of any clinical significant cardiovascular or neurological disease, cardiac, renal or hepatic insufficiency. (9) Known hypersensitivity to polyethylene glycols and/or ascorbic acid. (10) History or evidence of any clinically relevant electrocardiogram (ECG) abnormalities and/or uncontrolled hypertension. (11) Evidence of dehydration. (12) Any evidence for clinically significant abnormal sodium or potassium levels or other clinically significant plasma electrolyte disturbances. (13) Females who are not post-menopausal with a positive pregnancy test. Females not using reliable methods of birth control if not post-menopausal. (14) Clinically relevant findings on physical examination based on the Investigator’s judgement. (15) Clinically relevant deviations of laboratory parameters from reference ranges at screening or check-in evaluation. (16) Positive serology for chronic viral hepatitis or human immunodeficiency virus (HIV) at screening. (17) History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or check-in evaluations. (18) Subjects who are unwilling to comply with the provisions of the study protocol. (19) Concurrent participation in an investigational drug study or participation within 3 months of study entry. (20) Subject has a condition or is in a situation, which in the Investigator’s opinion may put the subject at significant risk, may confound the study results, or may interfere significantly. (21) Previous participation in the study. (22) Persons who are ordered to live in an institution on court or authority order.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the study is to investigate the effects of dose and taste-optimised, low volume polyethylene glycol (PEG)-based formulations after split-dosing, on stool output in healthy subjects, and stool output and bowel cleansing quality in subjects undergoing a screening colonoscopy.;Secondary Objective: The safety and tolerability of the optimised formulations will be assessed and compared with MOVIPREP®, a commercially available reference bowel preparation. This study will help to identify the optimum treatment regimen prior to Phase III clinical studies.;Primary end point(s): Part A and Part B: - Stool weight output within treatment group is above 2750 g. Part B only: - Cleansing success rate (grade A or B) based on the Harefield Cleansing Scale score will be summarised by treatment group. Pairwise comparison will be performed using the MOVIPREP® arm as a standard.;Timepoint(s) of evaluation of this end point: - Stool weight output: From first intake and for following 24 hours. - Cleansing success rate: During colonoscopy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A and Part B: - Tolerability (vomiting rate): Incidence of vomiting will be analysed descriptively. The response rate based on the incidence of vomiting will be compared between two treatment groups test. The MOVIPREP® arm will be taken as a reference, for each pair wise comparison (labelling vomiting incidence for MOVIPREP® is 1-10%). - Safety data (adverse events, laboratory tests, cardiovascular parameters, body weight) will be collected. - Tolerability questionnaire will be analysed, presenting summary statistics by treatment group. - Time and volume of IMP to reach a clear effluent. Part B only: - Segmental cleansing scores using Harefield Cleansing Scale for each of the five colon segments. - Pharmacokinetic evaluation of key active ingredients: ascorbate components and their metabolite (oxalic acid) in blood, urine and faeces and PEG3350 and electrolytes in faeces at defined time points, to demonstrate biological activities. Electrolytes in blood and urine will be quantified using clinical chemistry methods.;Timepoint(s) of evaluation of this end point: - Tolerability (vomiting rate): From first intake and for following 24 hours. - Safety data: From admission to unit to end of trial assessment. - Tolerability questionnaire will be completed after each intake. - Time and volume of IMP to reach a clear effluent: From first intake to end of trial assessment. - Segmental cleansing scores for each of the five colon segments: During colonoscopy. - Pharmacokinetic evaluation: From first intake to end of trial assessment. | — |
Countries
Germany
Contacts
Public ContactMedical Officer
Norgine Ltd
Outcome results
None listed