Trial Outcomes & Findings for Pyronaridine Artesunate-Ritonavir Drug-drug Interaction Study (NCT NCT01156389)
NCT ID: NCT01156389
Last Updated: 2023-02-03
Results Overview
Half-life and Tmax for pyronaridine, artesunate, DHA: Tmax - time of the maximum observed concentration Half life - apparent plasma terminal elimination half-life, computed as ln (2)/Kel Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
34 participants
Primary outcome timeframe
Until Day 50 for Arm A and until Day 43 for Arm B
Results posted on
2023-02-03
Participant Flow
Participant milestones
| Measure |
Arm A Ritonavir Plus Pyramax
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir
|
Arm B Pyramax
3 day treatment course of Pyramax
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
17
|
|
Overall Study
COMPLETED
|
13
|
16
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
Reasons for withdrawal
| Measure |
Arm A Ritonavir Plus Pyramax
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir
|
Arm B Pyramax
3 day treatment course of Pyramax
|
|---|---|---|
|
Overall Study
Elevated liver enzymes
|
4
|
0
|
|
Overall Study
Vomiting
|
0
|
1
|
Baseline Characteristics
Pyronaridine Artesunate-Ritonavir Drug-drug Interaction Study
Baseline characteristics by cohort
| Measure |
Arm A Ritonavir Plus Pyramax
n=17 Participants
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir
|
Arm B Pyramax
n=17 Participants
3 day treatment course of Pyramax
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42.3 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
43.7 years
STANDARD_DEVIATION 10.0 • n=7 Participants
|
43.0 years
STANDARD_DEVIATION 10.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
BMI
|
23.1 kg/m^2
STANDARD_DEVIATION 2.2 • n=5 Participants
|
24.2 kg/m^2
STANDARD_DEVIATION 2.6 • n=7 Participants
|
23.65 kg/m^2
STANDARD_DEVIATION 2.4 • n=5 Participants
|
PRIMARY outcome
Timeframe: Until Day 50 for Arm A and until Day 43 for Arm BPopulation: Number of subjects studied
Half-life and Tmax for pyronaridine, artesunate, DHA: Tmax - time of the maximum observed concentration Half life - apparent plasma terminal elimination half-life, computed as ln (2)/Kel Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.
Outcome measures
| Measure |
Arm A Ritonavir Plus Pyramax
n=17 Participants
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir
|
Arm B Pyramax
n=17 Participants
3 day treatment course of Pyramax
|
|---|---|---|
|
Pharmacokinetics Analysis: Half-life, Tmax
Pyronaridine half- life (adjusted to a common dose of 9.72 mg/kg)
|
384 hours
Standard Deviation 223.2
|
321.6 hours
Standard Deviation 69.6
|
|
Pharmacokinetics Analysis: Half-life, Tmax
Pyronaridine Tmax (adjusted to a common dose of 9.72 mg/kg)
|
2.32 hours
Standard Deviation 2.16
|
1.44 hours
Standard Deviation 0.36
|
|
Pharmacokinetics Analysis: Half-life, Tmax
Artesunate half-life (adjusted to common dose of 3.25 mg/kg)
|
0.425 hours
Standard Deviation 0.131
|
0.465 hours
Standard Deviation 0.197
|
|
Pharmacokinetics Analysis: Half-life, Tmax
Artesunate Tmax (adjusted to common dose of 3.25 mg/kg)
|
1.22 hours
Standard Deviation 0.69
|
0.84 hours
Standard Deviation 0.43
|
|
Pharmacokinetics Analysis: Half-life, Tmax
DHA half-life (adjusted for common 3.25 mg/kg artesunate dose)
|
2.27 hours
Standard Deviation 1.04
|
2.35 hours
Standard Deviation 0.900
|
|
Pharmacokinetics Analysis: Half-life, Tmax
DHA Tmax (adjusted for common 3.25 mg/kg artesunate dose)
|
1.90 hours
Standard Deviation 0.71
|
1.44 hours
Standard Deviation 0.403
|
PRIMARY outcome
Timeframe: Until Day 50 for Arm A and until Day 43 for Arm BPopulation: Number of subjects studied
Cmax for pyronaridine, artesunate, DHA: Cmax - maximum peak observed concentration Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.
Outcome measures
| Measure |
Arm A Ritonavir Plus Pyramax
n=17 Participants
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir
|
Arm B Pyramax
n=17 Participants
3 day treatment course of Pyramax
|
|---|---|---|
|
Pharmacokinetics Analysis: Cmax
Pyronaridine Cmax (adjusted to a common dose of 9.72 mg/kg)
|
480.2 ng/ml
Standard Deviation 145.1
|
407.5 ng/ml
Standard Deviation 167.1
|
|
Pharmacokinetics Analysis: Cmax
Artesunate Cmax (adjusted to common dose of 3.25 mg/kg)
|
128.2 ng/ml
Standard Deviation 91.2
|
108.7 ng/ml
Standard Deviation 49.1
|
|
Pharmacokinetics Analysis: Cmax
DHA Cmax (adjusted for common 3.25 mg/kg artesunate dose)
|
611.4 ng/ml
Standard Deviation 273.4
|
779.2 ng/ml
Standard Deviation 267.5
|
PRIMARY outcome
Timeframe: Until Day 50 for Arm A and until Day 43 for Arm BPopulation: Number of subjects studied
AUC0-tau, AUC0-∞ for pyronaridine, artesunate, DHA: AUC0-tau - area under the concentration-time curve from Hour 0 to the scheduled time of the next dose AUC0-∞ - area under the concentration-time curve from Hour 0 through the last quantifiable concentration time Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.
Outcome measures
| Measure |
Arm A Ritonavir Plus Pyramax
n=17 Participants
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir
|
Arm B Pyramax
n=17 Participants
3 day treatment course of Pyramax
|
|---|---|---|
|
Pharmacokinetics Analysis: AUC0-tau, AUC0-∞
Pyronaridine AUC0-tau (adjusted to a common dose of 9.72 mg/kg)
|
229 hours*ng/ml
Standard Deviation 82
|
222 hours*ng/ml
Standard Deviation 80
|
|
Pharmacokinetics Analysis: AUC0-tau, AUC0-∞
Pyronaridine AUC0-∞ (adjusted to a common dose of 9.72 mg/kg)
|
1244 hours*ng/ml
Standard Deviation 292
|
1318 hours*ng/ml
Standard Deviation 481
|
|
Pharmacokinetics Analysis: AUC0-tau, AUC0-∞
Artesunate AUC0-tau (adjusted to common dose of 3.25 mg/kg)
|
185.4 hours*ng/ml
Standard Deviation 105.6
|
150 hours*ng/ml
Standard Deviation 60
|
|
Pharmacokinetics Analysis: AUC0-tau, AUC0-∞
Artesunate AUC0-∞(adjusted to common dose of 3.25 mg/kg)
|
185.4 hours*ng/ml
Standard Deviation 105.6
|
149 hours*ng/ml
Standard Deviation 60
|
|
Pharmacokinetics Analysis: AUC0-tau, AUC0-∞
DHA AUC0-tau (adjusted for common 3.25 mg/kg artesunate dose)
|
1308 hours*ng/ml
Standard Deviation 544
|
1978 hours*ng/ml
Standard Deviation 622
|
|
Pharmacokinetics Analysis: AUC0-tau, AUC0-∞
DHA AUC0-∞ (adjusted for common 3.25 mg/kg artesunate dose)
|
1310 hours*ng/ml
Standard Deviation 545
|
1982 hours*ng/ml
Standard Deviation 628
|
SECONDARY outcome
Timeframe: Throughout the studyPopulation: Number of subjects studied
Including all the treatment emergent adverse events, the number of subjects discontinued due to adverse events and the number of subjects with serious adverse events.
Outcome measures
| Measure |
Arm A Ritonavir Plus Pyramax
n=17 Participants
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir
|
Arm B Pyramax
n=17 Participants
3 day treatment course of Pyramax
|
|---|---|---|
|
Summary of Treatment Emergent Adverse Events
Moderate treatment emergent adverse events
|
6 Participants
|
3 Participants
|
|
Summary of Treatment Emergent Adverse Events
Severe treatment emergent adverse events
|
0 Participants
|
0 Participants
|
|
Summary of Treatment Emergent Adverse Events
Mild treatment emergent adverse events
|
12 Participants
|
15 Participants
|
|
Summary of Treatment Emergent Adverse Events
Subjects discontinued due to adverse events
|
4 Participants
|
1 Participants
|
|
Summary of Treatment Emergent Adverse Events
Subjects with serious adverse events
|
0 Participants
|
0 Participants
|
Adverse Events
Arm A Ritonavir Plus Pyramax
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Arm B Pyramax
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm A Ritonavir Plus Pyramax
n=17 participants at risk
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir
|
Arm B Pyramax
n=17 participants at risk
3 day treatment course of Pyramax
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
17.6%
3/17 • Number of events 5 • up to Day 50 (end of study)
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.
|
11.8%
2/17 • Number of events 2 • up to Day 50 (end of study)
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
41.2%
7/17 • Number of events 9 • up to Day 50 (end of study)
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.
|
47.1%
8/17 • Number of events 9 • up to Day 50 (end of study)
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.
|
|
Gastrointestinal disorders
Nausea
|
17.6%
3/17 • Number of events 3 • up to Day 50 (end of study)
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.
|
17.6%
3/17 • Number of events 5 • up to Day 50 (end of study)
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.
|
|
General disorders
Fatigue
|
11.8%
2/17 • Number of events 4 • up to Day 50 (end of study)
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.
|
5.9%
1/17 • Number of events 1 • up to Day 50 (end of study)
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
Alanine aminotransferase increased
|
29.4%
5/17 • Number of events 5 • up to Day 50 (end of study)
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.
|
0.00%
0/17 • up to Day 50 (end of study)
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.
|
|
Nervous system disorders
Dizziness
|
11.8%
2/17 • Number of events 2 • up to Day 50 (end of study)
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.
|
23.5%
4/17 • Number of events 4 • up to Day 50 (end of study)
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.
|
|
Nervous system disorders
Headache
|
23.5%
4/17 • Number of events 4 • up to Day 50 (end of study)
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.
|
29.4%
5/17 • Number of events 6 • up to Day 50 (end of study)
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.
|
|
Vascular disorders
Hot flush
|
17.6%
3/17 • Number of events 3 • up to Day 50 (end of study)
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.
|
0.00%
0/17 • up to Day 50 (end of study)
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
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place