A Pharmacokinetic Study of PLENVU® in Healthy Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03437265

Acronym

PKPU

Enrollment

Registered

2018-02-19

Start date

2020-09-03

Completion date

2020-10-05

Last updated

2023-11-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pharmacokinetic

Brief summary

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

Detailed 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).

Interventions

DRUGPLENVU powder for oral solution

PLENVU Dose 1 (1 sachet) and PLENVU Dose 2 (2 sachets)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 30 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
AUC(0-inf) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1	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.
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)	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1	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.
AUC(0-last) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1	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.
Tmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1	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.
T1/2 (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1	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.
Cmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)	Blood samples were taken pre-dose and up to 60 hours after start of Dose 1	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.

Secondary

Measure	Time frame	Description
Time to Achieve Clear Effluent	Start of dose 1 to 60 hours	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
Timing and Number of Bowel Movements	Start of dose 1 to 60 hours	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.

Countries

United Kingdom

Participant flow

Participants by arm

Arm	Count
Overall Study All subjects who received at least a partial dose of IMP	19
Total	19

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Protocol Violation	6

Baseline characteristics

Characteristic	Overall Study
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	19 Participants
Age, Continuous	25.0 years
BMI	24.85 kg/m2 STANDARD_DEVIATION 3.896
Height	171.5 cm STANDARD_DEVIATION 10.92
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	3 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) White	13 Participants
Region of Enrollment United Kingdom	19 participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	10 Participants
Weight	73.82 kg STANDARD_DEVIATION 17.011

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 19
other Total, other adverse events	19 / 19
serious Total, serious adverse events	0 / 19

Outcome results

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.