Clinical trial NCT03437265
Conditions: Pharmacokinetic
Sponsor: Norgine
Start date: 2020-09-03; Completion date: 2020-10-05
Enrollment: 19 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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).

Arms: arm 1: 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.
Interventions: intervention 1: PLENVU powder for oral solution
Intervention descriptions: intervention 1: PLENVU Dose 1 (1 sachet) and PLENVU Dose 2 (2 sachets)

Protocol documents:
Prot_SAP_001.pdf: 
Sponsor/
 Confidential 
 
Protocol NER1006-03/2016 (PKPU) 
 Version 4.0 
19 MAY 2020 
  
 
 
Synopsis 
Sponsor: 
Norgine Ltd. 
Investigational Medicinal 
Product: 
PLENVU® Powder for Oral 
Solution 
EudraCT No.: 2017-003440-20 
 
Title of Study:  
A Pharmacokinetic Study of PLENVU® in Healthy Subjects 
Principal Investigator:  
 
Study Centre: 
 
Rationale: 
The purpose of this study is to determine if there is systemic exposure to components of the 
PLENVU (NER1006) formulation. If so, the plasma pharmacokinetic (PK) profiles for the 
components of PLENVU and their potential metabolites will be determined. In addition, this 
study aims to provide PK, safety and tolerability results to support the design of paediatric 
studies for PLENVU. 
Objectives: 
The primary objective is to characterise the pharmacokinetic (PK) profile of active ingredients 
of PLENVU®, PEG 3350, ascorbate and potential related substances/metabolites (oxalic acid 
and glycolic acid using high performance liquid chromatography-mass spectrometry 
[HPLC-MS], and ethylene glycol and diethylene glycol using gas chromatography-mass 
spectrometry [GC-MS]). 
The secondary objectives include the safety, tolerability and pharmacodynamics (PD) 
characterisation of PLENVU (1-Day Morning Only-Dosing) in healthy adult subjects. 
The exploratory objective of the study is to measure plasma concentrations of ethylene glycol 
and diethylene glycol using HPLC-MS. 
Methodology: 
This is a single centre, open-label, non-randomised, study in healthy adult male and 
non-pregnant, non-lactating female subjects to investigate the PK of PLENVU as a powder 
for oral solution formulation (PLENVU Dose 1 and PLENVU Dose 2). It is planned to enrol up 
to 18 subjects to ensure 12 evaluable subjects complete the study. Subjects will receive 
PLENVU on Day 1, with at least a 2 h period between the start of each dose. All subjects will 
receive the powder for oral solution formulations in the same order, i.e. PLENVU Dose 1, 
containing PEG 3350, sodium sulfate and electrolytes, followed by PLENVU Dose 2, 
containing sodium ascorbate, PEG 3350, ascorbic acid and electrolytes.  
Study Design: 
Subjects will be screened for inclusion in the study up to 28 days before dosing. Eligible 
subjects will be admitted in the afternoon (approximately 16:00) on the day before dosing 
(Day -1). Subjects will receive a standardised evening meal. At approximately 08:00 on Day 1, 
subjects will receive PLENVU Dose 1, reconstituted with water and made up to 16 US fl oz 
(473 mL), and 473 mL of additional water, both to be consumed over a period of 60 min after 
the start of Dose 1. Dose 2 will be administered at least 2 h after the start of Dose 1. At 
approximately 10:00, PLENVU Dose 2, reconstituted with water and made up to 16 US fl oz 
(473 mL), and 473 mL of additional water will be administered in the same manner as 
PLENVU Dose 1, and both to be consumed over a period of 60 min after the start of Dose 2. 
Additional water may be drunk ad libitum during and after each dose. Blood samples will be 


Sponsor/
 Confidential 
 
Protocol NER1006-03/2016 (PKPU) 
 Version 4.0 
19 MAY 2020 
  
 
taken at 1 and 2 h after the end of the evening meal on Day -1, 1 h before Dose 1 and serially 
from Dose 1 until 60 h after the start of dosing of PLENVU Dose 1, and safety assessments 
will be performed throughout the study. Subjects will be discharged from the clinic at 60 h 
after the start of dosing for PLENVU Dose 1, following completion of the PK and safety 
assessments. There will be a follow-up call 5 to 7 days after dosing to ensure the ongoing 
wellbeing of subjects.  
Number of Subjects Planned: 
It is planned to enrol a total of 18 subjects to ensure 12 evaluable subjects complete the study. 
A subject is considered evaluable if they have received 100% of each dose of PLENVU (i.e. 
Dose 1 and Dose 2), and 100% of the mandatory 473 mL additional water after each dose, 
have not vomited post-dose, and have sufficient PK, PD and safety data to meet the objectives 
of the study. 
Subjects withdrawn due to an investigational medicinal product (IMP)-related adverse event 
(AE), with the exception of IMP-related vomiting, or termination of the study will not be 
replaced. 
Subjects who are withdrawn for other reasons may be replaced at the discretion of the 
investigator and sponsor to ensure sufficient evaluable subjects. Up to 2 replacement subjects 
may be enrolled into the study. The maximum number of subjects that may be dosed is 20. 
Duration of Study: 
The estimated duration of the study is approximately 5 weeks. 
Main Inclusion Criteria: 
Healthy males and non-pregnant, non-lactating females aged 18 to 30 years. 
Body mass index 18.0 to 35.0 kg/m2. 
Investigational Medicinal Product, Dose and Mode of Administration: 
The following IMP will be used in this clinical study: 
Investigational Medicinal Product 
Dose and Route of Administration 
PLENVU Powder for Oral Solution  
Dose 1: Oral administration of 1 sachet (115.96 g) PLENVU 
Dose 1 (containing PEG 3350, sodium sulfate and 
electrolytes), to be 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. Additional water may be drunk ad libitum during and 
after the dose. 
Rest period: Dose 2 is administered at least 2 h after the start 
of Dose 1 
Dose 2: Oral administration of 2 sachets (101.91 g) PLENVU 
Dose 2 (containing sodium ascorbate, PEG 3350, ascorbic 
acid and electrolytes), to be 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 may be drunk ad libitum during and 
after the dose. 
Pharmacokinetic Assessments: 
Blood samples will be taken pre-dose and up to 60 h after the start of Dose 1 (baseline 
samples at 1 and 2 h after the end of the evening meal on Day -1 and at 1 h before Dose 1, 
and post-dose samples at 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 h for the first 10 h then at 12, 16, 20, 
24, 30, 36, 48 and 60 h) for the analysis of PEG 3350, ascorbate and potential related 
substances/metabolites (glycolic acid, oxalic acid, ethylene glycol and diethylene glycol). The 
following PK parameter estimates will be calculated for each analyte, where possible and 
appropriate. 
 
Cmax, Tlag, Tmax, AUC(0-last), AUC(0-inf), AUC(0-24), AUC%extrap, Lambda-z, T1/2