Trial Outcomes & Findings for Bioequivalence Trial of Pyronaridine Artesunate To-be-marketed Tablet to the Clinical Trial Reference Tablet (NCT NCT00682630)
NCT ID: NCT00682630
Last Updated: 2023-02-03
Results Overview
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
42 participants
Primary outcome timeframe
Sampling performed at predose at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each period
Results posted on
2023-02-03
Participant Flow
Participant milestones
| Measure |
Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets
Participants first received clinical trial reference 720:240 mg tablets on Day 0. After a washout period of 43 days, they then received to-be-marketed 720:240 mg tablets on Day 43, with a follow-up period of 42 days.
|
To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets
Participants first received to-be-marketed 720:240 mg tablets on Day 0. After a washout period of 43 days, they then received clinical trial reference 720:240 mg tablets on Day 43, with a follow-up period of 42 days.
|
|---|---|---|
|
First Intervention (Day 0)
STARTED
|
21
|
21
|
|
First Intervention (Day 0)
COMPLETED
|
20
|
21
|
|
First Intervention (Day 0)
NOT COMPLETED
|
1
|
0
|
|
Washout (43 Days)
STARTED
|
20
|
21
|
|
Washout (43 Days)
COMPLETED
|
18
|
19
|
|
Washout (43 Days)
NOT COMPLETED
|
2
|
2
|
|
Second Intervention (Day 43)
STARTED
|
18
|
19
|
|
Second Intervention (Day 43)
COMPLETED
|
18
|
19
|
|
Second Intervention (Day 43)
NOT COMPLETED
|
0
|
0
|
|
Follow-up (42 Days)
STARTED
|
18
|
19
|
|
Follow-up (42 Days)
COMPLETED
|
18
|
19
|
|
Follow-up (42 Days)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bioequivalence Trial of Pyronaridine Artesunate To-be-marketed Tablet to the Clinical Trial Reference Tablet
Baseline characteristics by cohort
| Measure |
Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets
n=21 Participants
Participants first received clinical trial reference 720:240 mg tablets on Day 0. After a washout period of 43 days, they then received to-be-marketed 720:240 mg tablets on Day 43, with a follow-up period of 42 days.
|
To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets
n=21 Participants
Participants first received to-be-marketed 720:240 mg tablets on Day 0. After a washout period of 43 days, they then received clinical trial reference 720:240 mg tablets on Day 43, with a follow-up period of 42 days.
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
34 years
STANDARD_DEVIATION 7.8 • n=93 Participants
|
33.5 years
STANDARD_DEVIATION 4.9 • n=4 Participants
|
33.8 years
STANDARD_DEVIATION 7.1 • n=27 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
BMI
|
23.5 kg/m^2
STANDARD_DEVIATION 1.4 • n=93 Participants
|
23.3 kg/m^2
STANDARD_DEVIATION 3.0 • n=4 Participants
|
23.4 kg/m^2
STANDARD_DEVIATION 2.0 • n=27 Participants
|
PRIMARY outcome
Timeframe: Sampling performed at predose at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each periodPopulation: Pharmacokinetic population
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
Outcome measures
| Measure |
Clinical Trial Reference Tablets
n=40 Participants
Participants who received clinical trial reference 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
To-Be-Marketed Tablets
n=39 Participants
Participants who received to-be-marketed 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
|---|---|---|
|
Pyronaridine Pharmacokinetics: Tmax, Half-life
Tmax
|
0.184 days
Standard Deviation 0.145
|
0.166 days
Standard Deviation 0.131
|
|
Pyronaridine Pharmacokinetics: Tmax, Half-life
Half-life
|
14.2 days
Standard Deviation 5.28
|
14.1 days
Standard Deviation 4.00
|
PRIMARY outcome
Timeframe: PP sampling performed at predose at at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each period AS, DHA sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each periodPopulation: Pharmacokinetic population
Cmax: maximum peak observed concentration
Outcome measures
| Measure |
Clinical Trial Reference Tablets
n=40 Participants
Participants who received clinical trial reference 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
To-Be-Marketed Tablets
n=39 Participants
Participants who received to-be-marketed 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
|---|---|---|
|
Pyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax
PP Cmax
|
512 ng/ml
Standard Deviation 183
|
533 ng/ml
Standard Deviation 190
|
|
Pyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax
AS Cmax
|
183 ng/ml
Standard Deviation 175
|
154 ng/ml
Standard Deviation 101
|
|
Pyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax
DHA Cmax
|
987 ng/ml
Standard Deviation 476
|
959 ng/ml
Standard Deviation 356
|
PRIMARY outcome
Timeframe: Sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each periodPopulation: Pharmacokinetic population
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
Outcome measures
| Measure |
Clinical Trial Reference Tablets
n=40 Participants
Participants who received clinical trial reference 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
To-Be-Marketed Tablets
n=39 Participants
Participants who received to-be-marketed 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
|---|---|---|
|
Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life
AS Tmax
|
0.488 hours
Standard Deviation 0.226
|
0.548 hours
Standard Deviation 0.279
|
|
Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life
DHA Tmax
|
1.14 hours
Standard Deviation 0.555
|
1.39 hours
Standard Deviation 0.823
|
|
Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life
AS half-life
|
0.549 hours
Standard Deviation 0.447
|
0.538 hours
Standard Deviation 0.717
|
|
Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life
DHA half-life
|
1.53 hours
Standard Deviation 0.452
|
1.84 hours
Standard Deviation 0.571
|
PRIMARY outcome
Timeframe: Sampling performed at predose at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each periodPopulation: Pharmacokinetic population
AUC0-last: Area under the concentration-time curve from time 0 (0 h) through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn AUC0-∞: Area under the concentration-time curve from time 0 (0 h) to infinity, computed using the linear trapezoidal rule as AUClast + CLQCT / Kel
Outcome measures
| Measure |
Clinical Trial Reference Tablets
n=40 Participants
Participants who received clinical trial reference 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
To-Be-Marketed Tablets
n=39 Participants
Participants who received to-be-marketed 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
|---|---|---|
|
Pyronaridine Pharmacokinetics: AUC0-last, AUC0-∞
AUC0-last
|
729 ng*day/ml
Standard Deviation 216
|
762 ng*day/ml
Standard Deviation 272
|
|
Pyronaridine Pharmacokinetics: AUC0-last, AUC0-∞
AUC0-∞
|
877 ng*day/ml
Standard Deviation 244
|
904 ng*day/ml
Standard Deviation 291
|
PRIMARY outcome
Timeframe: Sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each periodPopulation: Pharmacokinetic population
AUC0-last: Area under the concentration-time curve from time 0 (0 h) through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn AUC0-∞: Area under the concentration-time curve from time 0 (0 h) to infinity, computed using the linear trapezoidal rule as AUClast + CLQCT / Kel
Outcome measures
| Measure |
Clinical Trial Reference Tablets
n=40 Participants
Participants who received clinical trial reference 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
To-Be-Marketed Tablets
n=39 Participants
Participants who received to-be-marketed 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
|---|---|---|
|
Artesunate (AS) and Dihydroartemisinin (DHA): AUC0-last, AUC0-∞
AS AUC0-∞
|
155 ng*hr/ml
Standard Deviation 107
|
137 ng*hr/ml
Standard Deviation 83.9
|
|
Artesunate (AS) and Dihydroartemisinin (DHA): AUC0-last, AUC0-∞
AS AUC0-last
|
139 ng*hr/ml
Standard Deviation 106
|
121 ng*hr/ml
Standard Deviation 79.7
|
|
Artesunate (AS) and Dihydroartemisinin (DHA): AUC0-last, AUC0-∞
DHA AUC0-last
|
2150 ng*hr/ml
Standard Deviation 889
|
2120 ng*hr/ml
Standard Deviation 834
|
|
Artesunate (AS) and Dihydroartemisinin (DHA): AUC0-last, AUC0-∞
DHA AUC0-∞9
|
2166 ng*hr/ml
Standard Deviation 896
|
2143 ng*hr/ml
Standard Deviation 849
|
Adverse Events
To-Be-Marketed Tablets
Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths
Clinical Trial Reference Tablets
Serious events: 0 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
To-Be-Marketed Tablets
n=39 participants at risk
Participants who received to-be-marketed 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
Clinical Trial Reference Tablets
n=40 participants at risk
Participants who received clinical trial reference 720:240 mg tablets in either state each morning in either the first intervention (Day 0) or the second intervention (Day 43).
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
23.1%
9/39 • Number of events 9 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
22.5%
9/40 • Number of events 9 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.6%
1/39 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
0.00%
0/40 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Gastrointestinal disorders
Diarrhoea
|
23.1%
9/39 • Number of events 9 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
15.0%
6/40 • Number of events 6 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Gastrointestinal disorders
Dyspepsia
|
7.7%
3/39 • Number of events 3 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
2.5%
1/40 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Gastrointestinal disorders
Nausea
|
35.9%
14/39 • Number of events 14 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
37.5%
15/40 • Number of events 15 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Gastrointestinal disorders
Vomiting
|
38.5%
15/39 • Number of events 17 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
30.0%
12/40 • Number of events 15 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
General disorders
Pyrexia
|
2.6%
1/39 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
0.00%
0/40 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
2.6%
1/39 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
5.0%
2/40 • Number of events 2 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Investigations
Alanine aminotransferase increased
|
2.6%
1/39 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
5.0%
2/40 • Number of events 2 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/39 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
2.5%
1/40 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Nervous system disorders
Dizziness
|
2.6%
1/39 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
10.0%
4/40 • Number of events 4 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Nervous system disorders
Headache
|
7.7%
3/39 • Number of events 3 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
20.0%
8/40 • Number of events 8 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/39 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
2.5%
1/40 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Infections and infestations
Influenza
|
2.6%
1/39 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
0.00%
0/40 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
|
Infections and infestations
Viral pharyngitis
|
2.6%
1/39 • Number of events 1 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
0.00%
0/40 • 85 days (43 days Period 1, 42 days Period 2)
AE reporting was assessed through direct questioning.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place