Pharmacodynamic Evaluation of Stool Output Following Oral Administration of Various Low Volume PEG3350-based Gut Cleansing Solutions Using the Split Dose Intake in Healthy Subjects (OUT)

This study is to investigate the effect of various modified low volume polyethylene glycol (PEG) 3350 and ascorbic acid/ascorbate (PEG+ASC)-based gut cleansing solutions on stool output in healthy subjects. In addition, the study is to assess and compare the safety and tolerance of the modified PEG+ASC formulations following oral administration with the safety profile of MOVIPREP®.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: NER1006; Drug: NER1006; Drug: NER1006; Drug: NER1006; Drug: NER1006; Drug: NER1006; Drug: NER1006; Drug: Moviprep

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 1

Contacts and Locations

Study Locations

• Romania
  • Timisoara, Romania, 300244
    • Pierrel Research HP-RO-SRL
  • Timisoara, Romania
    • Pierrel Research HP-RO-SRL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject's written informed consent must be obtained prior to inclusion.
2. Healthy subjects with an age of 18 to 45 years.
3. Healthy subjects need to be without any history of clinical significant gastrointestinal symptoms by clinical judgement and without the presence of acute abdominal discomfort or symptoms.
4. Females must be surgically sterile, practicing true sexual abstinence or using an acceptable form of effective contraception throughout the study from the following list: contraceptive implants, injectables, 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. 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.
5. Willing, able and competent to complete the entire procedure and to comply with study instructions.

Exclusion Criteria:

1. Use of laxatives in the last 12 months or colon motility altering drugs in the last 6 months.
2. Use of any prescription or over-the-counter (OTC) medication within 4 weeks prior to the first dose of investigational drug (excluding hormonal contraception, and occasional use of nonsteroidal anti-inflammatory drugs [NSAID], acetaminophen or metamizole).
3. Donation or loss of 500 mL or more of blood within 8 weeks prior to the first dose of investigational drug.
4. Any evidence of the history or presence of organic or functional gastrointestinal conditions (e.g. chronic constipation, irritable bowel syndrome [IBS], inflammatory bowel disease [IBD]).
5. Exhibiting relevant abnormal gastrointestinal motility according to clinical judgement in the past or now.
6. History or presence of any clinically significant acute illness within the 4 weeks prior to the first dose of investigational drug based on clinical judgement at screening and check-in evaluation.
7. Known glucose-6-phosphatase dehydrogenase deficiency.
8. Known phenylketonuria.
9. History or evidence of any clinical significant systemic cardiovascular, hepatic, pulmonal, neurological, metabolic and/or renal organ dysfunction.
10. History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis), known hypersensitivity to polyethylene glycols and/or ascorbic acid.
11. History or evidence of any clinically relevant electrocardiogram (ECG) abnormalities and hypertension.
12. Evidence of dehydration.
13. Any evidence for abnormal sodium or potassium levels or clinically significant other electrolyte disturbances.
14. Females who are pregnant, having a positive pregnancy test at screening and/or admission to unit or planning a pregnancy. Females not using reliable methods of birth control.
15. Clinically relevant findings on physical examination based on Investigator's judgement.
16. Clinically relevant deviations of laboratory parameters from reference ranges at screening or check-in evaluation.
17. Positive serology for chronic viral hepatitis or human immunodeficiency virus (HIV) at screening.
18. 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.
19. Subjects who are unwilling to comply with the provisions of the study protocol.
20. Concurrent participation in an investigational drug study or participation within 3 month of study entry.
21. Subject has a condition or is in a situation, which in the Investigators opinion may put the subject at significant risk, may confound the study results, or may interfere significantly.
22. Previous participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A, arm 1; Evening dose 1 plus fixed morning dose	Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 9g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 75g PEG3350 plus 5.6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350 and 56.6g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate and 21.4g magnesium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 6g sodium sulphate and 33.9g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 29g PEG3350 and 4.8g sulphate and 23.3g ascorbic acid.
Experimental: Part A, arm 2; Evening dose 2 plus fixed morninf does	Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 9g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 75g PEG3350 plus 5.6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350 and 56.6g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate and 21.4g magnesium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 6g sodium sulphate and 33.9g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 29g PEG3350 and 4.8g sulphate and 23.3g ascorbic acid.
Experimental: Part A, arm 3; Evening dose 3 plus fixed morning dose	Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 9g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 75g PEG3350 plus 5.6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350 and 56.6g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate and 21.4g magnesium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 6g sodium sulphate and 33.9g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 29g PEG3350 and 4.8g sulphate and 23.3g ascorbic acid.
Active Comparator: Part A, arm 4; Moviprep	Drug: Moviprep; Reconstituted and administered in accordance with recommended split dose intake: one litre in the evening, one litre the following morning.
Experimental: Part B, arm 1; Fixed evening dose plus morning dose 1	Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 9g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 75g PEG3350 plus 5.6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350 and 56.6g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate and 21.4g magnesium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 6g sodium sulphate and 33.9g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 29g PEG3350 and 4.8g sulphate and 23.3g ascorbic acid.
Experimental: Part B, arm 2; Fixed evening dose plus morning dose 2	Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 9g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 75g PEG3350 plus 5.6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350 and 56.6g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate and 21.4g magnesium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 6g sodium sulphate and 33.9g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 29g PEG3350 and 4.8g sulphate and 23.3g ascorbic acid.
Experimental: Part B, arm 3; Fixed evening dose plus morning dose 3	Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 9g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 75g PEG3350 plus 5.6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350 and 56.6g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate and 21.4g magnesium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 6g sodium sulphate and 33.9g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 29g PEG3350 and 4.8g sulphate and 23.3g ascorbic acid.
Experimental: Part B, arm 4; Fixed evening dose plus alternative morning dose	Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 100g PEG3350 plus 9g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose of 750mL solution containing 75g PEG3350 plus 5.6g sodium sulphate. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate, 20.1g ascorbic acid.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350 and 56.6g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 33.9g sodium ascorbate and 21.4g magnesium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 40g PEG3350, 6g sodium sulphate and 33.9g sodium ascorbate.; Drug: NER1006; Single evening dose containing formulation selected from Part A of study. Single morning dose containing 29g PEG3350 and 4.8g sulphate and 23.3g ascorbic acid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Variable	Stool weight output generated from the start of intake for the following 24 hours.	36 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PEG3350 concentration	Concentration of PEG3350 in blood, urine and faeces.	96 Hours
Sulphate concentration	Concentration of PEG3350 in blood, urine and faeces.	96 hours
Ascorbic acid concentration	Concentration of ascorbic acid in blood, urine and faeces.	96 hours
Electrolytes concentration	Concentration of electrolytes in blood, urine and faeces.	96 hours
Safety profile	Spontaneouly reported adverse events will be recorded throughout the study	96 hours

Collaborators and Investigators

• Sponsor: Norgine
• Collaborators: Pierrel Research Europe GmbH
• Investigators: Principal Investigator: Rodica Cinca, MD, Pierrel Research

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: April 15, 2013
• First Submitted That Met QC Criteria: April 15, 2013
• First Posted (Estimate): April 18, 2013

Study Record Updates

• Last Update Posted (Estimate): April 18, 2013
• Last Update Submitted That Met QC Criteria: April 15, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Laxative; PEG3350; Moviprep; Stool Output
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: NER1006-01/2011 (OUT)