Trial Outcomes & Findings for Human Mass Balance Study of Pyronaridine (NCT NCT01383109)

Last Updated: 2022-01-26

Results Overview

Radioactivity recovery in urine as a percent of the administered dose. Continuous collection of samples was performed through 168 hours post-dose, with intermittent 48 hour collections occurring thereafter

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

6 participants

Primary outcome timeframe

2064 hours

Results posted on

2022-01-26

Participant Flow

Participant milestones

Participant milestones
Measure	Pyronaridine 14C-labeled Pyronaridine: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Human Mass Balance Study of Pyronaridine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pyronaridine n=6 Participants 14C-labeled Pyronaridine: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Age, Continuous	48.8 years STANDARD_DEVIATION 4.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	6 Participants n=5 Participants
Height	180.3 cm STANDARD_DEVIATION 8.2 • n=5 Participants
Weight	78.0 kg STANDARD_DEVIATION 7.4 • n=5 Participants
BMI	24.1 kg/m^2 STANDARD_DEVIATION 2.6 • n=5 Participants

PRIMARY outcome

Timeframe: 2064 hours

Population: The pharmacokinetic population consisted of all subjects without any major violations of any inclusion or exclusion criteria, who received a dose of the study drug, had not received any unauthorised drug(s) which could have adversely affected the pharmacokinetic analysis, and had evaluable pharmacokinetic data.

Outcome measures

Outcome measures
Measure	Pyronaridine n=6 Participants 14C-labeled Pyronaridine: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 0-4h	0.09 % administered dose Standard Deviation 0.02
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 4-8h	0.16 % administered dose Standard Deviation 0.08
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 8-24h	0.60 % administered dose Standard Deviation 0.20
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 24-48h	0.71 % administered dose Standard Deviation 0.08
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 48-72h	0.67 % administered dose Standard Deviation 0.24
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 72-96h	0.63 % administered dose Standard Deviation 0.10
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 96-120h	0.55 % administered dose Standard Deviation 0.08
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 120-144h	0.55 % administered dose Standard Deviation 0.09
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 144-168h	0.60 % administered dose Standard Deviation 0.23
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 168-336h	3.87 % administered dose Standard Deviation 0.69
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 336-384h	2.38 % administered dose Standard Deviation 0.60
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 384-504h	2.38 % administered dose Standard Deviation 0.60
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 504-552h	0.84 % administered dose Standard Deviation 0.37
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 552-672h	1.81 % administered dose Standard Deviation 0.69
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 672-720h	0.61 % administered dose Standard Deviation 0.23
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 720-840h	1.34 % administered dose Standard Deviation 0.58
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 840-888h	0.46 % administered dose Standard Deviation 0.23
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 888-1008h	1.11 % administered dose Standard Deviation 0.45
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 1008-1056h	0.42 % administered dose Standard Deviation 0.14
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 1056-1344h	2.08 % administered dose Standard Deviation 0.61
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 1344-1392h	0.27 % administered dose Standard Deviation 0.07
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 1392-1680h	1.42 % administered dose Standard Deviation 0.34
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 1680-1728h	0.20 % administered dose Standard Deviation 0.04
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 1728-2016h	1.12 % administered dose Standard Deviation 0.26
Analysis of 14C-Pyronaridine Total Radioactivity in Urine 2016-2064h	0.17 % administered dose Standard Deviation 0.04

PRIMARY outcome

Timeframe: 2064 hours

Radioactivity recovery in feces as a percent of the administered dose. Continuous collection of samples was performed through 168 hours post-dose, with intermittent 48 hour collections occurring thereafter

Outcome measures

Outcome measures
Measure	Pyronaridine n=6 Participants 14C-labeled Pyronaridine: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 24-48h	7.31 % administered dose Standard Deviation 6.12
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 48-72h	12.78 % administered dose Standard Deviation 8.45
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 72-96h	5.83 % administered dose Standard Deviation 3.65
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 96-120h	4.53 % administered dose Standard Deviation 1.68
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 120-144h	2.11 % administered dose Standard Deviation 1.68
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 144-168h	2.03 % administered dose Standard Deviation 2.13
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 168-336h	7.89 % administered dose Standard Deviation 2.01
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 336-384h	1.40 % administered dose Standard Deviation 0.78
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 384-504h	2.69 % administered dose Standard Deviation 1.42
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 504-552h	0.76 % administered dose Standard Deviation 0.39
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 552-672h	1.58 % administered dose Standard Deviation 0.66
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 672-720h	0.51 % administered dose Standard Deviation 0.17
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 720-840h	1.01 % administered dose Standard Deviation 0.30
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 840-888h	0.30 % administered dose Standard Deviation 0.11
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 888-1008h	0.70 % administered dose Standard Deviation 0.31
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 1008-1056h	0.26 % administered dose Standard Deviation 0.16
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 1056-1344h	1.23 % administered dose Standard Deviation 0.53
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 1344-1392h	0.15 % administered dose Standard Deviation 0.08
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 1392-1680h	0.68 % administered dose Standard Deviation 0.13
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 1680-1728h	0.09 % administered dose Standard Deviation 0.03
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 1728-2016h	0.41 % administered dose Standard Deviation 0.18
Analysis of 14C-Pyronaridine Total Radioactivity in Feces 2016-2064h	0.07 % administered dose Standard Deviation 0.01

SECONDARY outcome

Timeframe: 42 days

Pharmacokinetic Parameters: AUC0-t: area under the plasma concentration-time curve from Hour 0 through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was collected AUC0-∞: area under the plasma concentration-time curve from Hour 0 to infinity PK sampling performed at predose, 0.5, 1, 2, 4, 8, 12 and 24 hours, and 2, 4, 6, 7, 14, 21, 28, 35 and 42 days post-dose

Outcome measures

Outcome measures
Measure	Pyronaridine n=6 Participants 14C-labeled Pyronaridine: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Total Radioactivity in Blood: AUC0-t, AUC0-∞ AUC0-t	1834 day*ng-eq/ml Standard Deviation 530
Total Radioactivity in Blood: AUC0-t, AUC0-∞ AUC0-∞	3731 day*ng-eq/ml Standard Deviation 1303

SECONDARY outcome

Timeframe: 42 days

Pharmacokinetic Parameters: Cmax: maximum observed peak observed concentration PK sampling performed at predose, 0.5, 1, 2, 4, 8, 12 and 24 hours, and 2, 4, 6, 7, 14, 21, 28, 35 and 42 days post-dose

Outcome measures

Outcome measures
Measure	Pyronaridine n=6 Participants 14C-labeled Pyronaridine: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Total Radioactivity in Blood: Cmax	271 ng-eq/ml Standard Deviation 113

SECONDARY outcome

Timeframe: 42 days

Pharmacokinetic Parameters: Half-life: computed as ln (2) / Kel Tmax: time to maximum concentration PK sampling performed at predose, 0.5, 1, 2, 4, 8, 12 and 24 hours, and 2, 4, 6, 7, 14, 21, 28, 35 and 42 days post-dose

Outcome measures

Outcome measures
Measure	Pyronaridine n=6 Participants 14C-labeled Pyronaridine: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Total Radioactivity in Blood: Half-life, Tmax Half-life	33.5 days Standard Deviation 11.4
Total Radioactivity in Blood: Half-life, Tmax Tmax	0.111 days Standard Deviation 0.111

Adverse Events

Pyronaridine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Pyronaridine n=6 participants at risk 14C-labeled Pyronaridine: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Musculoskeletal and connective tissue disorders Myalgia	33.3% 2/6 • Number of events 2 • 87 days The condition of each subject was monitored throughout the study. In addition, any signs and symptoms were observed and elicited at least once a day by open questioning, such as "How have you been feeling since you were last asked?". Subjects were also encouraged to report spontaneously any adverse events during the study.
Investigations Elevated liver enzymes	16.7% 1/6 • Number of events 1 • 87 days The condition of each subject was monitored throughout the study. In addition, any signs and symptoms were observed and elicited at least once a day by open questioning, such as "How have you been feeling since you were last asked?". Subjects were also encouraged to report spontaneously any adverse events during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	16.7% 1/6 • Number of events 1 • 87 days The condition of each subject was monitored throughout the study. In addition, any signs and symptoms were observed and elicited at least once a day by open questioning, such as "How have you been feeling since you were last asked?". Subjects were also encouraged to report spontaneously any adverse events during the study.

Additional Information

Jansik Shin

Shin Poong Pharmaceutical Co., Ltd.

Phone: +82-2-2189-3468

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place