A Pharmacokinetic Study of PLENVU® in Healthy Subjects

NCT03437265 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: NER1006-03/2016 (PKPU)2017-003440-20
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetic

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (2)

• Timing and Number of Bowel Movements

  Start of dose 1 to 60 hours

• Time to Achieve Clear Effluent

  Start of dose 1 to 60 hours

Study Arms (1)

PLENVU powder for oral solution

EXPERIMENTAL

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

Interventions

PLENVU powder for oral solution DRUG

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

Also known as: NER1006

PLENVU powder for oral solution

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Norgine: lead
• Quotient Sciences: collaborator

Study Sites (1)

Quotient Sciences (Quotient),

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

Solutions

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Limitations and Caveats

In addition to PEG 3350, glycolic acid and ascorbic acid, PK parameters were to be determined for oxalic acid, ethylene glycol and diethylene glycol. However, this was not done, as no quantifiable concentrations of oxalic acid (LLOQ \<10.0 μg/mL), diethylene glycol (LLOQ \<2.50 μg/mL), or ethylene glycol (LLOQ \<2.50 μg/mL) were observed. Diarrhoea was expected as it is the intended pharmacodynamic effect of PLENVU bowel preparation.

Results Point of Contact

• Title: Lucy Clayton
• Organization: Norgine

LClayton@norgine.com

+441895826669

Study Officials

• Philip Evans, MBChB, MRCS

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: February 19, 2018
• Study Start: September 3, 2020
• Primary Completion: October 5, 2020
• Study Completion: October 5, 2020
• Last Updated: November 29, 2023
• Results First Posted: November 3, 2021

Record last verified: 2023-11

Locations

GB (1)