A Pharmacokinetic Study of PLENVU® in Healthy Subjects

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Pharmacokinetic Study of PLENVU® in Healthy Subjects

Conditions
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Pharmacokinetic

Intervention / Treatment
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* Drug: PLENVU powder for oral solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or non-pregnant, non-lactating healthy females Age 18 to 30 years BMI of 18.0 to 35.0 kg/m2 Must be willing and able to communicate and participate in the whole study Must provide written informed consent Must agree to use an adequate method of contraception Exclusion Criteria: Subjects who have received any Investigational Medicinal Product (IMP) in a clinical research study within the previous 3 months Subjects who are study site employees, or immediate family members of a study site or sponsor employee Subjects who have previously been enrolled in this study. History of any drug or alcohol abuse in the past 2 years 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) Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months Females who are pregnant or lactating (all female subjects must have a negative urine pregnancy test at screening and admission). Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator at screening Evidence of dehydration or abnormal electrolyte levels. Clinical evidence or suspicion of significant dehydration at admission/pre-dose. History or evidence of any clinically relevant ECG abnormality and hypertension Positive drugs of abuse test result Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or psychiatric disorder, as judged by the investigator History or presence of organic or functional gastrointestinal conditions (e.g. chronic constipation, inflammatory bowel disease or irritable bowel syndrome) Previous or current relevant abnormal gastrointestinal motility according to clinical judgement 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 History of any of the contraindications mentioned in the PLENVU Summary of Product Characteristics (SmPC) Clinically relevant findings on physical examination based on investigator judgement Donation or loss of greater than 500 mL of blood within the previous 8 weeks 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. Use of laxatives and gastrointestinal motility altering drug in the last 3 months Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection Subjects who are ordered to live in an institution on court or authority order Failure to satisfy the investigator of fitness to participate for any other reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLENVU powder for oral solution<br>Dose 1: Oral administration of 1 sachet (115.96 g) PLENVU Dose 1, reconstituted with water and made up to 473 mL and 473 mL of additional water to be consumed; both to be consumed over a period of 60 min after the start of Dose 1. Dose 2: Oral administration of 2 sachets (101.91 g) comprising PLENVU Dose 2, reconstituted with water and made up to 473 mL and 473 mL of additional water to be consumed; both to be consumed over a period of 60 min after the start of Dose 2. Additional water was permitted ad libitum during and after each dose. | Drug: PLENVU powder for oral solution<br>* PLENVU Dose 1 (1 sachet) and PLENVU Dose 2 (2 sachets)<br>* Other names: NER1006;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 |