Trial Outcomes & Findings for Study of the Safety of Intravenous Artesunate (NCT NCT00292942)
NCT ID: NCT00292942
Last Updated: 2018-10-25
Results Overview
The general strategy of the safety analysis was to examine the clinical tolerability and laboratory safety parameter data and determine if there were any trends amongst the dose levels concerning all AEs and drug related AEs.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
up to 21 days
Results posted on
2018-10-25
Participant Flow
A total of 47 subjects were screened over the 3 dose escalation cohorts of the study. Twenty-six subjects were enrolled and received IV AS at the USUHS, Clinical Pharmacology Unit (CPU), Bethesda, MD
Participant milestones
| Measure |
Placebo
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
7
|
7
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Study of the Safety of Intravenous Artesunate
Baseline characteristics by cohort
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=7 Participants
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
n=7 Participants
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
36.0 years
STANDARD_DEVIATION 10.41 • n=5 Participants
|
43.2 years
STANDARD_DEVIATION 12.02 • n=7 Participants
|
35.3 years
STANDARD_DEVIATION 9.96 • n=5 Participants
|
35.0 years
STANDARD_DEVIATION 11.86 • n=4 Participants
|
37.2 years
STANDARD_DEVIATION 10.95 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Subjects with >1 race
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Height (cm)
|
173.68 cm
STANDARD_DEVIATION 7.598 • n=5 Participants
|
172.97 cm
STANDARD_DEVIATION 3.634 • n=7 Participants
|
173.14 cm
STANDARD_DEVIATION 12.472 • n=5 Participants
|
175.34 cm
STANDARD_DEVIATION 2.519 • n=4 Participants
|
173.82 cm
STANDARD_DEVIATION 7.348 • n=21 Participants
|
|
Weight (kg)
|
80.33 kg
STANDARD_DEVIATION 8.390 • n=5 Participants
|
76.53 kg
STANDARD_DEVIATION 11.114 • n=7 Participants
|
81.03 kg
STANDARD_DEVIATION 12.681 • n=5 Participants
|
77.80 kg
STANDARD_DEVIATION 5.912 • n=4 Participants
|
78.96 kg
STANDARD_DEVIATION 9.445 • n=21 Participants
|
|
Body Mass Index (kg/m^2)
|
26.68 kg/m^2
STANDARD_DEVIATION 2.917 • n=5 Participants
|
25.50 kg/m^2
STANDARD_DEVIATION 2.828 • n=7 Participants
|
26.89 kg/m^2
STANDARD_DEVIATION 2.270 • n=5 Participants
|
25.30 kg/m^2
STANDARD_DEVIATION 1.628 • n=4 Participants
|
26.09 kg/m^2
STANDARD_DEVIATION 2.386 • n=21 Participants
|
PRIMARY outcome
Timeframe: up to 21 daysThe general strategy of the safety analysis was to examine the clinical tolerability and laboratory safety parameter data and determine if there were any trends amongst the dose levels concerning all AEs and drug related AEs.
Outcome measures
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=7 Participants
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
n=7 Participants
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Number of Participants With AEs
All AEs · Subjects with 1 AE
|
3 Participants
|
3 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With AEs
All AEs · Subjects with 2 AEs
|
3 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With AEs
All AEs · Subjects with ≥3 AEs
|
0 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With AEs
Drug Related AEs · Subjects with 1 AE
|
2 Participants
|
3 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With AEs
Drug Related AEs · Subjects with 2 AEs
|
2 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With AEs
Drug Related AEs · Subjects with ≥3 AEs
|
0 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With AEs
Drug Related AEs · No AEs
|
2 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With AEs
All AEs · No AEs
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: up to 21 daysPopulation: As the intended, compassionate use dose of Intravenous Artesunate will be 2.4 mg/kg for the treatment of individuals with severe malaria, a comparison was performed between the frequency of AEs reported for the placebo control subjects and those treated with the 2.0 mg/kg dose of Intravenous Artesunate.
Comparison of number of participants with AEs reported for the placebo control and those treated with the 2.0 mg/kg of IV AS to access safety and tolerability
Outcome measures
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Dysguesia
|
1 Participants
|
4 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Dizziness
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Headache
|
1 Participants
|
3 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Pruritus Generalized
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Tenderness
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Venipuncture Site Inflammation
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Back Pain
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Parethesia
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Parosmia
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Erythema
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Eye Pain
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants With AEs Occurring in Greater Frequency in the 2.0 mg/kg IV AS Group Then in the Placebo Group to Access Safety and Tolerability of AS
Muscle Strain
|
0 Participants
|
1 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: screening, on Day -1, on Days 1, 2, and 3, and at each follow-up visitCardiovascular Responses: Number of participants with changes in blood pressure and heart rate after infusion to determine change from baseline
Outcome measures
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=7 Participants
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
n=7 Participants
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion
Systolic BP change of at least 20mmHg · No significant change
|
5 Participants
|
5 Participants
|
6 Participants
|
6 Participants
|
|
Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion
Heart Rate change of at least 15bpm · Increase
|
4 Participants
|
4 Participants
|
6 Participants
|
3 Participants
|
|
Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion
Systolic BP change of at least 20mmHg · Increase
|
1 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion
Systolic BP change of at least 20mmHg · Decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion
Heart Rate change of at least 15bpm · Decrease
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion
Heart Rate change of at least 15bpm · No significant change
|
2 Participants
|
2 Participants
|
1 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusionFor artesunic acid, AUC0-last was determine for each dose; as well as the total area under the curve (AUClastTOTAL), calculated as the sum of AUClast for each of the doses (ng\*hr/mL)
Outcome measures
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=6 Participants
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC last 3 (ng.hr/mL)
|
933 ng*hr/mL
Standard Deviation 239
|
1627 ng*hr/mL
Standard Deviation 957
|
4374 ng*hr/mL
Standard Deviation 2362
|
—
|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC last TOTAL (ng.hr/mL)
|
3027 ng*hr/mL
Standard Deviation 1158
|
5683 ng*hr/mL
Standard Deviation 550
|
14733 ng*hr/mL
Standard Deviation 5846
|
—
|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC24 1 (ng.hr/mL)
|
1368 ng*hr/mL
Standard Deviation 912
|
2325 ng*hr/mL
Standard Deviation 721
|
5766 ng*hr/mL
Standard Deviation 2121
|
—
|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC24 2 (ng.hr/mL)
|
978 ng*hr/mL
Standard Deviation 648
|
1746 ng*hr/mL
Standard Deviation 247
|
5272 ng*hr/mL
Standard Deviation 2089
|
—
|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC24 3 (ng.hr/mL)
|
935 ng*hr/mL
Standard Deviation 301
|
1880 ng*hr/mL
Standard Deviation 795
|
4379 ng*hr/mL
Standard Deviation 2361
|
—
|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC last 1 (ng.hr/mL)
|
1162 ng*hr/mL
Standard Deviation 656
|
2421 ng*hr/mL
Standard Deviation 755
|
4631 ng*hr/mL
Standard Deviation 2402
|
—
|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC last 2 (ng.hr/mL)
|
932 ng*hr/mL
Standard Deviation 524
|
1636 ng*hr/mL
Standard Deviation 342
|
5728 ng*hr/mL
Standard Deviation 1980
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusionFor the predicted concentration at the time of dose administration (C0) was determine for each dose (ng/mL)
Outcome measures
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=6 Participants
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL)
C0 1
|
14840 ng/mL
Standard Deviation 10902
|
29056 ng/mL
Standard Deviation 12850
|
53503 ng/mL
Standard Deviation 33017
|
—
|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL)
C0 2
|
11992 ng/mL
Standard Deviation 8311
|
17265 ng/mL
Standard Deviation 3590
|
66380 ng/mL
Standard Deviation 32973
|
—
|
|
Range of Pharmacokinetic Parameters for Artesunic Acid After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL)
C0 3
|
10408 ng/mL
Standard Deviation 1851
|
23417 ng/mL
Standard Deviation 10200
|
54674 ng/mL
Standard Deviation 43261
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusionFor DHA, AUC24, and AUClast were calculated for each dose, as well as the total area under the curve extrapolated to infinite time (AUC∞TOTAL), calculated as the sum of AUC24 for each dose +C24/λz.
Outcome measures
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=6 Participants
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Range of Pharmacokinetic Parameters for Dihydroartemisinin (DHA) After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC24 1
|
1982 ng*hr/mL
Standard Deviation 377
|
4122 ng*hr/mL
Standard Deviation 809
|
8992 ng*hr/mL
Standard Deviation 3355
|
—
|
|
Range of Pharmacokinetic Parameters for Dihydroartemisinin (DHA) After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC24 2
|
1865 ng*hr/mL
Standard Deviation 512
|
3509 ng*hr/mL
Standard Deviation 970
|
8122 ng*hr/mL
Standard Deviation 2750
|
—
|
|
Range of Pharmacokinetic Parameters for Dihydroartemisinin (DHA) After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC24 3
|
2204 ng*hr/mL
Standard Deviation 524
|
3748 ng*hr/mL
Standard Deviation 646
|
8571 ng*hr/mL
Standard Deviation 2817
|
—
|
|
Range of Pharmacokinetic Parameters for Dihydroartemisinin (DHA) After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC last 1
|
1954 ng*hr/mL
Standard Deviation 367
|
4065 ng*hr/mL
Standard Deviation 771
|
8842 ng*hr/mL
Standard Deviation 3265
|
—
|
|
Range of Pharmacokinetic Parameters for Dihydroartemisinin (DHA) After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC last 2
|
1847 ng*hr/mL
Standard Deviation 516
|
3394 ng*hr/mL
Standard Deviation 974
|
8011 ng*hr/mL
Standard Deviation 2780
|
—
|
|
Range of Pharmacokinetic Parameters for Dihydroartemisinin (DHA) After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC last 3
|
2171 ng*hr/mL
Standard Deviation 519
|
3701 ng*hr/mL
Standard Deviation 647
|
8405 ng*hr/mL
Standard Deviation 2715
|
—
|
|
Range of Pharmacokinetic Parameters for Dihydroartemisinin (DHA) After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng*hr/mL)
AUC oo TOTAL
|
6051 ng*hr/mL
Standard Deviation 1074
|
11379 ng*hr/mL
Standard Deviation 2128
|
25685 ng*hr/mL
Standard Deviation 8715
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusionCmax was calculated after single 2.0, 4.0 and 8.0 mg/kg dose of Artesunate daily for 3 days (ng/mL)
Outcome measures
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=6 Participants
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL)
Cmax 1
|
1735 ng/mL
Standard Deviation 547
|
3015 ng/mL
Standard Deviation 882
|
6057 ng/mL
Standard Deviation 2456
|
—
|
|
Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL)
Cmax 2
|
1710 ng/mL
Standard Deviation 715
|
2923 ng/mL
Standard Deviation 1050
|
5943 ng/mL
Standard Deviation 2110
|
—
|
|
Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL)
Cmax 3
|
2358 ng/mL
Standard Deviation 634
|
2933 ng/mL
Standard Deviation 810
|
5762 ng/mL
Standard Deviation 3426
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusionTmax was calculated after single 2.0, 4.0 and 8.0 mg/kg dose of Artesunate daily for 3 days (hr)
Outcome measures
| Measure |
Placebo
n=6 Participants
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 Participants
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=6 Participants
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr)
Tmax 1 (hr)
|
0.244 hr
Standard Deviation 0.132
|
0.208 hr
Standard Deviation 0.137
|
0.208 hr
Standard Deviation 0.137
|
—
|
|
Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr)
Tmax 2 (hr)
|
0.167 hr
Standard Deviation 0.129
|
0.208 hr
Standard Deviation 0.137
|
0.181 hr
Standard Deviation 0.238
|
—
|
|
Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr)
Tmax 3 (hr)
|
0.122 hr
Standard Deviation 0.104
|
0.292 hr
Standard Deviation 0.102
|
0.250 hr
Standard Deviation 0.129
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
2 mg/kg Intravenous Artesunate
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
4 mg/kg Intravenous Artesunate
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
8 mg/kg Intravenous Artesunate
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=6 participants at risk
Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate.
Placebo: Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
|
2 mg/kg Intravenous Artesunate
n=6 participants at risk
2 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
4 mg/kg Intravenous Artesunate
n=7 participants at risk
4 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
8 mg/kg Intravenous Artesunate
n=7 participants at risk
8 mg/kg of Intravenous artesunate
Intravenous Artesunate: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
|
|---|---|---|---|---|
|
Nervous system disorders
Dysgeusia
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
66.7%
4/6 • Number of events 4 • up to 21 days
|
85.7%
6/7 • Number of events 6 • up to 21 days
|
85.7%
6/7 • Number of events 6 • up to 21 days
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
50.0%
3/6 • Number of events 3 • up to 21 days
|
28.6%
2/7 • Number of events 2 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Nervous system disorders
Parosmia
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Nervous system disorders
Syncope vasovagal
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Blood and lymphatic system disorders
Anemia
|
50.0%
3/6 • Number of events 3 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
57.1%
4/7 • Number of events 4 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Infections and infestations
Bacteriuria
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Eye disorders
Asthenopia
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Eye disorders
Eye pain
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Eye disorders
Photophobia
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
General disorders
Fatigue
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
General disorders
Venipuncture site
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
General disorders
Inflammation
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Investigations
Body temperature increased
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Vascular disorders
Flushing
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
|
Vascular disorders
Hot flush
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Gastrointestinal disorders
Lip pain
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/6 • up to 21 days
|
16.7%
1/6 • Number of events 1 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/6 • up to 21 days
|
0.00%
0/6 • up to 21 days
|
0.00%
0/7 • up to 21 days
|
14.3%
1/7 • Number of events 1 • up to 21 days
|
Additional Information
Louis Cantilena, Jr., MD, PhD
Uniformed Services University of the Health Sciences
Phone: 301-295-0016
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place