Trial Outcomes & Findings for A Pharmacokinetic Study of PLENVU® in Healthy Subjects (NCT NCT03437265)
NCT ID: NCT03437265
Last Updated: 2023-11-29
Results Overview
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.
COMPLETED
PHASE1
19 participants
Blood samples were taken pre-dose and up to 60 hours after start of Dose 1
2023-11-29
Participant Flow
Participant milestones
| Measure |
Overall Study
Healthy adult subjects given PLENVU powder for oral solution: PLENVU Dose 1 (1 sachet) and PLENVU Dose 2 (2 sachets)
|
|---|---|
|
Overall Study
STARTED
|
19
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Overall Study
Healthy adult subjects given PLENVU powder for oral solution: PLENVU Dose 1 (1 sachet) and PLENVU Dose 2 (2 sachets)
|
|---|---|
|
Overall Study
Protocol Violation
|
6
|
Baseline Characteristics
A Pharmacokinetic Study of PLENVU® in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Overall Study
n=19 Participants
All subjects who received at least a partial dose of IMP
|
|---|---|
|
Region of Enrollment
United Kingdom
|
19 participants
n=5 Participants
|
|
BMI
|
24.85 kg/m2
STANDARD_DEVIATION 3.896 • n=5 Participants
|
|
Height
|
171.5 cm
STANDARD_DEVIATION 10.92 • n=5 Participants
|
|
Weight
|
73.82 kg
STANDARD_DEVIATION 17.011 • n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
25.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Blood samples were taken pre-dose and up to 60 hours after start of Dose 1Population: PK population 1: all evaluable subjects who had a minimum of 1 valid post-dose analytical result for PK parameter estimation and who satisfied the following criterion for at least 1 profile: no relevant protocol deviations which may have impacted the study objectives with respect to the PK endpoints.
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.
Outcome measures
| Measure |
Overall Study
n=13 Participants
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
Tmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
PEG 3350
|
3.00 hours
Interval 1.97 to 4.03
|
|
Tmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Glycolic acid
|
9.00 hours
Interval 4.0 to 36.07
|
|
Tmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Ascorbic acid
|
5.00 hours
Interval 4.0 to 6.0
|
PRIMARY outcome
Timeframe: Blood samples were taken pre-dose and up to 60 hours after start of Dose 1Population: PK population 1: all evaluable subjects who had a minimum of 1 valid post-dose analytical result for PK parameter estimation and who satisfied the following criterion for at least 1 profile: no relevant protocol deviations which may have impacted the study objectives with respect to the PK endpoints.
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.
Outcome measures
| Measure |
Overall Study
n=13 Participants
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
T1/2 (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
PEG 3350
|
3.58 hours
Geometric Coefficient of Variation 14.3
|
|
T1/2 (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Glycolic acid
|
4.63 hours
Geometric Coefficient of Variation 0
|
|
T1/2 (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Ascorbic acid
|
11.62 hours
Geometric Coefficient of Variation 270
|
PRIMARY outcome
Timeframe: Blood samples were taken pre-dose and up to 60 hours after start of Dose 1Population: PK population 1: all evaluable subjects who had a minimum of 1 valid post-dose analytical result for PK parameter estimation and who satisfied the following criterion for at least 1 profile: no relevant protocol deviations which may have impacted the study objectives with respect to the PK endpoints.
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.
Outcome measures
| Measure |
Overall Study
n=13 Participants
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
Cmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
PEG 3350
|
1010 ng/mL
Geometric Coefficient of Variation 42.5
|
|
Cmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Glycolic acid
|
528 ng/mL
Geometric Coefficient of Variation 113.0
|
|
Cmax (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Ascorbic Acid (μg/mL)
|
59.1 ng/mL
Geometric Coefficient of Variation 26.1
|
PRIMARY outcome
Timeframe: Blood samples were taken pre-dose and up to 60 hours after start of Dose 1Population: PK population 1: all evaluable subjects who had a minimum of 1 valid post-dose analytical result for PK parameter estimation and who satisfied the following criterion for at least 1 profile: no relevant protocol deviations which may have impacted the study objectives with respect to the PK endpoints.
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.
Outcome measures
| Measure |
Overall Study
n=13 Participants
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
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)
PEG 3350
|
7220 ng.h/mL
Geometric Coefficient of Variation 31.7
|
|
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)
Glycolic acid
|
3820 ng.h/mL
Geometric Coefficient of Variation 53.1
|
|
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)
Ascorbic acid (μg.h/mL)
|
359 ng.h/mL
Geometric Coefficient of Variation 17.3
|
PRIMARY outcome
Timeframe: Blood samples were taken pre-dose and up to 60 hours after start of Dose 1Population: PK population 1: all evaluable subjects who had a minimum of 1 valid post-dose analytical result for PK parameter estimation and who satisfied the following criterion for at least 1 profile: no relevant protocol deviations which may have impacted the study objectives with respect to the PK endpoints.
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.
Outcome measures
| Measure |
Overall Study
n=13 Participants
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
AUC(0-last) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
PEG 3350
|
7140 ng.h/mL
Geometric Coefficient of Variation 32.2
|
|
AUC(0-last) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Glycolic acid
|
9020 ng.h/mL
Geometric Coefficient of Variation 51.5
|
|
AUC(0-last) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Ascorbic acid (μg.h/mL)
|
437 ng.h/mL
Geometric Coefficient of Variation 24.0
|
PRIMARY outcome
Timeframe: Blood samples were taken pre-dose and up to 60 hours after start of Dose 1Population: PK population 1: all evaluable subjects who had a minimum of 1 valid post-dose analytical result for PK parameter estimation and who satisfied the following criterion for at least 1 profile: no relevant protocol deviations which may have impacted the study objectives with respect to the PK endpoints.
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.
Outcome measures
| Measure |
Overall Study
n=13 Participants
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
AUC(0-inf) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
PEG 3350
|
7340 ng.h/mL
Geometric Coefficient of Variation 31.1
|
|
AUC(0-inf) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Gycolic acid
|
6900 ng.h/mL
Geometric Coefficient of Variation 0
|
|
AUC(0-inf) (PEG 3350, Baseline-corrected Glycolic Acid and Baseline-corrected Ascorbic Acid)
Ascorbic acid (μg.h/mL)
|
397 ng.h/mL
Geometric Coefficient of Variation 23.9
|
SECONDARY outcome
Timeframe: Start of dose 1 to 60 hoursPopulation: Pharmacodynamic (PD) analysis set: subjects who received both doses and had sufficient PD data for at least 1 time point
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.
Outcome measures
| Measure |
Overall Study
n=13 Participants
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
Timing and Number of Bowel Movements
24 - 48 hours · ≥10 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 0 bowel movements
|
10 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 1 bowel movement
|
3 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 2 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 4 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 5 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 6 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 7 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 8 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 9 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · ≥10 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 0 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 1 bowel movement
|
0 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 2 bowel movements
|
1 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 3 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 4 bowel movements
|
1 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 5 bowel movements
|
2 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 6 bowel movements
|
1 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 7 bowel movements
|
4 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 8 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · 9 bowel movements
|
1 Participants
|
|
Timing and Number of Bowel Movements
0-6 hours · ≥10 bowel movements
|
3 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 0 bowel movements
|
1 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 1 bowel movement
|
4 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 2 bowel movements
|
4 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 3 bowel movements
|
4 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 4 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 5 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 6 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 7 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 8 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · 9 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
6 - 12 hours · ≥10 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 0 bowel movements
|
10 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 1 bowel movement
|
3 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 2 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 3 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 4 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 5 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 6 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 7 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 8 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · 9 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
12 - 24 hours · ≥10 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 0 bowel movements
|
10 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 1 bowel movement
|
3 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 2 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 3 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 4 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 5 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 6 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 7 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 8 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
24 - 48 hours · 9 bowel movements
|
0 Participants
|
|
Timing and Number of Bowel Movements
48 - 60 hours · 3 bowel movements
|
0 Participants
|
SECONDARY outcome
Timeframe: Start of dose 1 to 60 hoursPopulation: PD (pharmacodynamic) analysis set: subjects who received both doses and had sufficient PD data for at least 1 time point
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
Outcome measures
| Measure |
Overall Study
n=13 Participants
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
Time to Achieve Clear Effluent
Time to clear effluent (A)
|
226.0 minutes
Interval 98.0 to 310.0
|
|
Time to Achieve Clear Effluent
Time to turbid contents (B)
|
165.5 minutes
Interval 58.0 to 410.0
|
Adverse Events
Overall Study
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Overall Study
n=19 participants at risk
All subjects who received at least a partial dose of IMP.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
100.0%
19/19 • Number of events 19 • Screening (Day -28 to -2) to post study follow-up (Day 6 to 8)
Adverse Events were recorded from the time of providing written informed consent until discharge from the study at the follow-up visit/call. During each study visit, subjects were questioned directly regarding the occurrence of any adverse medical event according to the schedule in the clinical database.
|
|
Gastrointestinal disorders
Nausea
|
42.1%
8/19 • Number of events 8 • Screening (Day -28 to -2) to post study follow-up (Day 6 to 8)
Adverse Events were recorded from the time of providing written informed consent until discharge from the study at the follow-up visit/call. During each study visit, subjects were questioned directly regarding the occurrence of any adverse medical event according to the schedule in the clinical database.
|
|
Gastrointestinal disorders
Proctalgia
|
15.8%
3/19 • Number of events 3 • Screening (Day -28 to -2) to post study follow-up (Day 6 to 8)
Adverse Events were recorded from the time of providing written informed consent until discharge from the study at the follow-up visit/call. During each study visit, subjects were questioned directly regarding the occurrence of any adverse medical event according to the schedule in the clinical database.
|
|
Gastrointestinal disorders
Vomiting
|
15.8%
3/19 • Number of events 3 • Screening (Day -28 to -2) to post study follow-up (Day 6 to 8)
Adverse Events were recorded from the time of providing written informed consent until discharge from the study at the follow-up visit/call. During each study visit, subjects were questioned directly regarding the occurrence of any adverse medical event according to the schedule in the clinical database.
|
|
General disorders
Feeling hot
|
5.3%
1/19 • Number of events 1 • Screening (Day -28 to -2) to post study follow-up (Day 6 to 8)
Adverse Events were recorded from the time of providing written informed consent until discharge from the study at the follow-up visit/call. During each study visit, subjects were questioned directly regarding the occurrence of any adverse medical event according to the schedule in the clinical database.
|
|
Nervous system disorders
Headache
|
5.3%
1/19 • Number of events 1 • Screening (Day -28 to -2) to post study follow-up (Day 6 to 8)
Adverse Events were recorded from the time of providing written informed consent until discharge from the study at the follow-up visit/call. During each study visit, subjects were questioned directly regarding the occurrence of any adverse medical event according to the schedule in the clinical database.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
5.3%
1/19 • Number of events 1 • Screening (Day -28 to -2) to post study follow-up (Day 6 to 8)
Adverse Events were recorded from the time of providing written informed consent until discharge from the study at the follow-up visit/call. During each study visit, subjects were questioned directly regarding the occurrence of any adverse medical event according to the schedule in the clinical database.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The agreement between Norgine and Quotient Sciences states that Quotient have no publication rights.
- Publication restrictions are in place
Restriction type: OTHER