Pharmacodynamic and Clinical Evaluation of Dose and Taste-optimised Low Volume PEG-based Bowel Cleansing Solutions Using the Split-dosing Intake Regimen in Healthy Subjects and in Subjects Undergoing Screening Colonoscopy

A study to assess the pharmacodynamics, safety and tolerability of a PEG-based bowel cleansing solution (MOVIPREP®)

Study Overview

• Status: Completed
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: MOVIPREP; Drug: NER1006

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Parexel International GmbH
  • Berlin, Germany, 14050
    • PAREXEL International Early Product Development Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subject's written informed consent must be obtained prior to inclusion.
• Subjects age 40 to 70 years.

• Part B only: Subjects willing to undergoing a screening colonoscopy, where the subject:

  1. is between 40 and 70 years of age and has a known personal or familial risk of colon neoplasia,or
  2. is aged 55 to 70.
• Part A: 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.
• 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).
• Willing, able and competent to complete the entire procedure and to comply with study instructions.
• Ferrous sulphate should be stopped at least one week prior to study medication.

Exclusion Criteria:

• Part A only: Subjects undergoing screening colonoscopy.
• Presence of current clinically significant functional gastrointestinal (GI) disorder (e.g. gastric emptying disorder, chronic constipation, irritable bowel syndrome [IBS]).
• Regular use of laxatives or colon motility altering drugs in the last month.
• Donation or loss of 500 mL or more of blood within 8 weeks prior to the first dose of investigational drug.
• Any history or current presence of ileus, gastrointestinal (GI) obstruction or perforation , GI tract cancer, inflammatory bowel disease (IBD) or colonic resection.
• Known glucose-6-phosphatase dehydrogenase deficiency.
• Known phenylketonuria.
• History or evidence of any clinical significant cardiovascular or neurological disease, cardiac, renal or hepatic insufficiency.
• Known hypersensitivity to polyethylene glycols and/or ascorbic acid.
• History or evidence of any clinically relevant electrocardiogram (ECG) abnormalities and/or uncontrolled hypertension.
• Evidence of dehydration.
• Any evidence for clinically significant abnormal sodium or potassium levels or other clinically significant plasma electrolyte disturbances.
• Females who are not post-menopausal with a positive pregnancy test. Females not using reliable methods of birth control if not post-menopausal.
• Clinically relevant findings on physical examination based on the Investigator's judgement.
• Clinically relevant deviations of laboratory parameters from reference ranges at screening or check-in evaluation.
• Positive serology for chronic viral hepatitis or human immunodeficiency virus (HIV) at screening.
• 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.
• Subjects who are unwilling to comply with the provisions of the study protocol.
• Concurrent participation in an investigational drug study or participation within 3 months of study entry.
• 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.
• Previous participation in the study.
• Persons who are ordered to live in an institution on court or authority order

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A, arm 1; Evening dose of TF048. Morning dose of TF043	Drug: NER1006
Experimental: Part A, arm 2; Evening dose of TF043. Morning dose of TF048	Drug: NER1006
Experimental: Part A, arm 3; Evening dose of TF047. Morning dose of TF043	Drug: NER1006
Active Comparator: Part A, arm 4; MOVIPREP (Both evening and morning dose)	Drug: MOVIPREP
Experimental: Part B, arm 1; IMP selected based on the optimal dosing sequence and volume identified from Part A	Drug: NER1006
Experimental: Part B, arm 2; IMP as used in Part B, arm 1, with a differing amount of additional clear fluid being consumed	Drug: NER1006
Active Comparator: Part B, arm 3; IMP as used in Part B, arm 1, except for a reduced amount of ascorbate	Drug: NER1006
Experimental: Part B, arm 4; MOVIPREP used in both evening and morning dose	Drug: MOVIPREP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool weight output	Stool weight output generated by the IMP from the start of the intake on the evening of Day 1 and the following 24 hours	36 hours post-dose
Cleansing success rate	The cleansing success rate (grade A or B according to the Harefield Cleansing Scale)	36 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of medication (vomiting rate)	The patient's tolerability to the study medication by measuring their vomiting rate for both parts A and B	36 hours post-dose
EQ 5D patient questionnaire outcome (Part A only)	Patients to use the EQ 5D patient questionnaire to assess their study medication for part A	36 hours post-dose
Cleansing scores for each colon segment	The segmental cleansing scores for each of the five colon segments	36 hours post-dose
Time and volume of IMP to reach a clear effluent	The time and volume taken for the IMP to reach a clear effluent	36 hours post-dose
Ascorbate concentration	Concentration of ascorbate components and its metabolites (such as dehydroascorbic acid and oxalic acid)	36 hours post-dose
Electrolytes concentration	Concentration of electrolytes in blood, urine and faeces	36 hours post-dose
PEG3350 concentration	Presence of PEG3350 in faeces, at defined time points, to demonstrate biological activities	36 hours post-dose

Collaborators and Investigators

• Sponsor: Norgine
• Investigators: Principal Investigator: Rudiger Kornberger, MD, Parexel

Publications and helpful links

General Publications

• Clayton LB, Tayo B, Halphen M, Kornberger R. Novel 1 L polyethylene glycol-based bowel preparation (NER1006): proof of concept assessment versus standard 2 L polyethylene glycol with ascorbate - a randomized, parallel group, phase 2, colonoscopist-blinded trial. BMC Gastroenterol. 2019 May 30;19(1):79. doi: 10.1186/s12876-019-0988-y.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: October 19, 2012
• First Submitted That Met QC Criteria: October 23, 2012
• First Posted (Estimate): October 26, 2012

Study Record Updates

• Last Update Posted (Estimate): November 20, 2014
• Last Update Submitted That Met QC Criteria: November 19, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: NER1006-01/2012 (OPT)