A Pharmacokinetic Study of PLENVU® in Healthy Subjects

Pharmacokinetic Clinical Trial

— PKPU  

Official title:

A Pharmacokinetic Study of PLENVU® in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03437265
• Other study ID #: NER1006-03/2016 (PKPU)
• Secondary ID: 2017-003440-20
• Status: Completed
• Phase: Phase 1
• Start date: September 3, 2020
• Est. completion date: October 5, 2020

Study information

• Verified date: November 2023
• Source: Norgine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study characterises the pharmacokinetic (PK) profile of the active ingredients of PLENVU (NER1006) and their related substances/metabolites. Subjects will receive PLENVU.

Description:

PLENVU is a novel, low volume (1 L) PEG 3350 and ascorbate based bowel preparation that has been developed to provide whole bowel cleansing. Studies have shown that formulating the osmotically active agents sodium ascorbate/ascorbic acid (also known as vitamin C) and sodium sulfate in combination with PEG 3350 enable a reduction in the volume of the PEG-based lavage solution.

PLENVU has a dual formulation containing an initial majority PEG dose followed by a majority ascorbate dose to maximise the overall effectiveness. This novel formulation addresses the challenges faced by patients to comply with drinking higher volume, 2 and 3 L, preparations.

The purpose of this study is to determine if there is systemic exposure to components of the PLENVU formulation (PEG 3350, ascorbate and potential related substances/metabolites (oxalic acid, glycolic acid, ethylene glycol and diethylene glycol).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: October 5, 2020
• Est. primary completion date: October 5, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

1. Healthy males or non-pregnant, non-lactating healthy females

2. Age 18 to 30 years

3. BMI of 18.0 to 35.0 kg/m2

4. Must be willing and able to communicate and participate in the whole study

5. Must provide written informed consent

6. Must agree to use an adequate method of contraception

Exclusion Criteria:

1. Subjects who have received any Investigational Medicinal Product (IMP) in a clinical research study within the previous 3 months

2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee

3. Subjects who have previously been enrolled in this study.

4. History of any drug or alcohol abuse in the past 2 years

5. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)

6. Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening

7. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months

8. Females who are pregnant or lactating (all female subjects must have a negative urine pregnancy test at screening and admission).

9. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening

10. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator at screening

11. Evidence of dehydration or abnormal electrolyte levels. Clinical evidence or suspicion of significant dehydration at admission/pre-dose.

12. History or evidence of any clinically relevant ECG abnormality and hypertension

13. Positive drugs of abuse test result

14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results

15. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or psychiatric disorder, as judged by the investigator

16. History or presence of organic or functional gastrointestinal conditions (e.g. chronic constipation, inflammatory bowel disease or irritable bowel syndrome)

17. Previous or current relevant abnormal gastrointestinal motility according to clinical judgement

18. History or presence of any clinically significant acute illness within 28 days prior to the first dose of IMP based on clinical judgement at screening or admission

19. History of any of the contraindications mentioned in the PLENVU Summary of Product Characteristics (SmPC)

20. Clinically relevant findings on physical examination based on investigator judgement

21. Donation or loss of greater than 500 mL of blood within the previous 8 weeks

22. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than hormonal contraception and occasional use of non-steroidal anti-inflammatory drugs [NSAIDs] and paracetamol) or herbal remedies in the 28 days before IMP administration Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor.

23. Use of laxatives and gastrointestinal motility altering drug in the last 3 months

24. Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

25. Subjects who are ordered to live in an institution on court or authority order

26. Failure to satisfy the investigator of fitness to participate for any other reason

Related Conditions & MeSH terms

• Pharmacokinetic

Intervention

Drug:
• PLENVU powder for oral solution
PLENVU Dose 1 (1 sachet) and PLENVU Dose 2 (2 sachets)

Locations

Country	Name	City	State
United Kingdom	Quotient Sciences (Quotient),	Ruddington	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
Norgine	Quotient Sciences

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Time of maximum observed concentration (of PEG3350, and glycolic acid and ascorbic acid corrected for baseline levels), calculated from individual plasma concentrations of the pharmacokinetic (PK) population.	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1
Primary	T1/2 (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Apparent elimination half-life (of PEG3350, and glycolic acid and ascorbic acid corrected for baseline levels), calculated from individual plasma concentrations of the PK population.	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1
Primary	Cmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	The mean maximum observed concentration (of PEG3350, and glycolic acid and ascorbic acid corrected for baseline levels), calculated from individual plasma concentrations of the PK population.	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1
Primary	Area Under the Curve From 0 Time to 24 h Post-dose (AUC[0-24]) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Area under the curve from 0 time to 24 h post-dose (of PEG3350, and glycolic acid and ascorbic acid corrected for baseline levels), calculated from individual plasma concentrations of the PK population.	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1
Primary	AUC(0-last) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Area under the curve from 0 time to the last measurable concentration (of PEG3350, and glycolic acid and ascorbic acid corrected for baseline levels), calculated from individual plasma concentrations of the PK population.	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1
Primary	AUC(0-inf) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Area under the curve from 0 time extrapolated to infinity (of PEG3350, and glycolic acid and ascorbic acid corrected for baseline levels), calculated from individual plasma concentrations of the PK population.	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1
Secondary	Timing and Number of Bowel Movements	Pharmacodynamic outcome. The time of each bowel movement will be recorded for each subject, and the number of bowel movements after each dose per subject will be derived.	Start of dose 1 to 60 hours
Secondary	Time to Achieve Clear Effluent	Pharmacodynamic outcome. Scoring was according to a 4-point scale (adapted from the stool characteristics rating tool described by Hsu et al, Adv Dig Med. 2016; 3 (3):144-147).; A. Clear contents (may be coloured but able to visualise the bottom of the toilet bowl) B. Turbid contents C. Opaque contents (dark and murky) D. Any solid/semi-solid faecal material (irrespective of size) in the toilet bowl	Start of dose 1 to 60 hours