Malaria, Malaria, Cerebral
Conditions
Keywords
artesunate, artemisinin, falciparum
Brief summary
The purpose of this study is to establish the safety, tolerability, and pharmacokinetics of a multiple dose of the antimalarial drug artesunate.
Detailed description
This study was a Phase 1b, randomized, double-blind, placebo-controlled trial using multiple ascending doses of intravenous artensunate (AS) to determine it's safety, tolerability, and PK in healthy subjects. Subjects were screened within 21 days of dosing. At the screening visit, subject underwent baseline assessments: vital signs were recorded; a physical examination, urinalysis, urine drug screen, and urine pregnancy test were performed; a complete blood cell count (CBC) with differential and indices, reticulocyte count, coagulation markers, and blood chemistry assessments were performed and medical and medication history was collected. Eligible subjects were scheduled for a 6-hour pre-dose electrocardiogram (ECG) and vital sign assessment with measurements taken at approx. the same times as Day 1 (dosing day). On Day 0, subjects were admitted to the clinical pharmacology unit to begin the inpatient phase of the study. Subjects had a brief physical examination and all procedures for the inpatient stay were reviewed. On Day 1, pre-dose vital signs and ECG were performed. Subjects then received study drug or placebo by IV bolus infusion. Subjects were closely monitored by evaluating hemodynamic measurements, periodic ECGs, and assessment of spontaneously reported AEs. Blood was drawn for blood count and chemistry analysis 6h and 24h after each dose. PK blood samples were drawn pre-dose and approx. 5min, 20min, 40min, 1h, 2h, 4h, 6h, and 24h after each dose. On Days 2 and 3 subjects received their second and third doses, respectively, of study drug or placebo with the same monitoring and laboratory measurements as for the first dose. Subjects were discharged 24 hours after the 3rd dose of drug or placebo and were followed as outpatients on Days 7, 10, and 15.
Interventions
Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
DRUGPlacebo
Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
Sponsors
Walter Reed Army Institute of Research (WRAIR)
U.S. Army Medical Research and Development Command
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult males and non-pregnant, non-lactating females * Have a normal ECG that may include benign PAC's and PVC's, 1st degree AV block, 2nd degree AV block, Wenckebach * Have a normal blood pressure (BP) and heart rate (HR). These will be measured after resting supine for about 3 minutes. Normal BP is defined as less than 140 mm Hg systolic and less than 90 mm Hg diastolic. Normal baseline HR is 50 to 90 bpm without symptoms. * Body mass index between 18 and 29 kg/m\*\*2 or, if out of range, not clinically significant (within 15% of their ideal body weight). * Be able to verbalize understanding of the consent form, provide written informed consent and verbalize willingness to complete study procedures * Have a physical examination that demonstrates no clinically significant contraindication for participating in the study. This would include documentation of any abnormal movements suggesting neurological pathology and ECG tracings to document an abnormalities in cardiac conduction * If female, have a negative serum pregnancy test at screening and urine pregnancy test on pre-admission and admission, or be postmenopausal, or have had a hysterectomy, or have been sterilized, AND, if still able to bear children, agree to practice effective contraception for the duration of the study and for a period of 12 weeks after stopping study drug. * Active duty participants must be on leave during the inpatient phase of the study.
Exclusion criteria
* Have received any investigational drug or vaccine in the period 0 to 16 weeks before entry to the study. * Have been on a liquid protein diet in the last year * Have any clinically important physical findings, laboratory abnormalities, or histories of Rx or OTC drug use that may, in the judgement of a study investigator, impact study interpretation or affect subject safety * Have used any prescription drugs within 14 days prior to admission or most non-prescription drugs including herbals or dietary supplements within 7 days prior to admission (at the investigator's discretion). * Existence of any surgical or medical condition that, in the judgement of the clinical investigator, might interfere with the distribution, metabolism or excretion of the drug * Presence of history of drug allergy requiring treatment. Hay fever is allowed unless it is active or has required treatment within the previous 2 months * Donation or loss of greater than 400 ml of blood in the period 0 to 12 weeks before entry to the study. * Serious adverse reaction or hypersensitivity to any drug, particularly artemisinin derivatives * CAGE (screening test for alcoholism) postitive (2 out of 4 criteria) or has a history of recent alcohol abuse * Use of illicit drugs * Family history (in 1st degree relatives) of sudden cardiac death or prolonged QT/QTc syndrome * History of seizure (excluding febrile seizures in childhood), episodes of unexplained syncope, or trouble with balance, undiagnosed hearing deficits, and other neurological disorder * History of severe psychiatric disorder or hospitalization for severe psychiatric disorder * Current job or personal habit of reversed sleep-wake cycle * History of cardiac disease to include cardiomyopathy, valvular disease, arrhythmia, ischemia, or enlarged heart * Presence of hepatitis B surface antigen (Hbs-Ag), hepatitis C antibody (antiHCV) or HIV type 1 at screening * A finding or history of hematuria (excluding menses-related hematuria) during subject screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With AEs | up to 21 days | 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. |
| 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 | up to 21 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusion | For 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) |
| 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) | Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusion | For the predicted concentration at the time of dose administration (C0) was determine for each dose (ng/mL) |
| 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) | Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion | For 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. |
| Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr) | Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion | Tmax was calculated after single 2.0, 4.0 and 8.0 mg/kg dose of Artesunate daily for 3 days (hr) |
| Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL) | Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion | Cmax was calculated after single 2.0, 4.0 and 8.0 mg/kg dose of Artesunate daily for 3 days (ng/mL) |
| Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion | screening, on Day -1, on Days 1, 2, and 3, and at each follow-up visit | Cardiovascular Responses: Number of participants with changes in blood pressure and heart rate after infusion to determine change from baseline |
Countries
United States
Participant flow
Recruitment details
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
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| 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) | 6 |
| 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) | 7 |
| 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) | 7 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 2 mg/kg Intravenous Artesunate | Total | Placebo | 8 mg/kg Intravenous Artesunate | 4 mg/kg Intravenous Artesunate |
|---|---|---|---|---|---|
| Age, Continuous | 43.2 years STANDARD_DEVIATION 12.02 | 37.2 years STANDARD_DEVIATION 10.95 | 36.0 years STANDARD_DEVIATION 10.41 | 35.0 years STANDARD_DEVIATION 11.86 | 35.3 years STANDARD_DEVIATION 9.96 |
| Body Mass Index (kg/m^2) | 25.50 kg/m^2 STANDARD_DEVIATION 2.828 | 26.09 kg/m^2 STANDARD_DEVIATION 2.386 | 26.68 kg/m^2 STANDARD_DEVIATION 2.917 | 25.30 kg/m^2 STANDARD_DEVIATION 1.628 | 26.89 kg/m^2 STANDARD_DEVIATION 2.27 |
| Height (cm) | 172.97 cm STANDARD_DEVIATION 3.634 | 173.82 cm STANDARD_DEVIATION 7.348 | 173.68 cm STANDARD_DEVIATION 7.598 | 175.34 cm STANDARD_DEVIATION 2.519 | 173.14 cm STANDARD_DEVIATION 12.472 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 9 Participants | 4 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Subjects with >1 race | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 12 Participants | 2 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 6 Participants | 26 Participants | 6 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 24 Participants | 5 Participants | 7 Participants | 6 Participants |
| Weight (kg) | 76.53 kg STANDARD_DEVIATION 11.114 | 78.96 kg STANDARD_DEVIATION 9.445 | 80.33 kg STANDARD_DEVIATION 8.39 | 77.80 kg STANDARD_DEVIATION 5.912 | 81.03 kg STANDARD_DEVIATION 12.681 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 7 | 7 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 7 |
Outcome results
Primary
Number of Participants With AEs
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.
Time frame: up to 21 days
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Number of Participants With AEs | All AEs | Subjects with 2 AEs | 3 Participants |
| Placebo | Number of Participants With AEs | Drug Related AEs | Subjects with 2 AEs | 2 Participants |
| Placebo | Number of Participants With AEs | All AEs | Subjects with ≥3 AEs | 0 Participants |
| Placebo | Number of Participants With AEs | All AEs | No AEs | 0 Participants |
| Placebo | Number of Participants With AEs | All AEs | Subjects with 1 AE | 3 Participants |
| Placebo | Number of Participants With AEs | Drug Related AEs | Subjects with ≥3 AEs | 0 Participants |
| Placebo | Number of Participants With AEs | Drug Related AEs | Subjects with 1 AE | 2 Participants |
| Placebo | Number of Participants With AEs | Drug Related AEs | No AEs | 2 Participants |
| 2 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | No AEs | 0 Participants |
| 2 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with 1 AE | 3 Participants |
| 2 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with 2 AEs | 0 Participants |
| 2 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with ≥3 AEs | 3 Participants |
| 2 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | No AEs | 0 Participants |
| 2 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with 1 AE | 3 Participants |
| 2 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with 2 AEs | 1 Participants |
| 2 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with ≥3 AEs | 2 Participants |
| 4 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with 1 AE | 0 Participants |
| 4 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with ≥3 AEs | 3 Participants |
| 4 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with 2 AEs | 1 Participants |
| 4 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | No AEs | 2 Participants |
| 4 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with 2 AEs | 1 Participants |
| 4 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with 1 AE | 1 Participants |
| 4 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with ≥3 AEs | 4 Participants |
| 4 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | No AEs | 2 Participants |
| 8 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with ≥3 AEs | 3 Participants |
| 8 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | No AEs | 1 Participants |
| 8 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with ≥3 AEs | 2 Participants |
| 8 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with 1 AE | 2 Participants |
| 8 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | No AEs | 0 Participants |
| 8 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with 2 AEs | 2 Participants |
| 8 mg/kg Intravenous Artesunate | Number of Participants With AEs | Drug Related AEs | Subjects with 2 AEs | 2 Participants |
| 8 mg/kg Intravenous Artesunate | Number of Participants With AEs | All AEs | Subjects with 1 AE | 2 Participants |
Primary
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
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
Time frame: up to 21 days
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 4 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 3 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 2 mg/kg Intravenous Artesunate | 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 | 1 Participants |
Secondary
Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion
Cardiovascular Responses: Number of participants with changes in blood pressure and heart rate after infusion to determine change from baseline
Time frame: screening, on Day -1, on Days 1, 2, and 3, and at each follow-up visit
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| 2 mg/kg Intravenous Artesunate | 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 |
| 2 mg/kg Intravenous Artesunate | 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 |
| 2 mg/kg Intravenous Artesunate | 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 |
| 2 mg/kg Intravenous Artesunate | 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 |
| 2 mg/kg Intravenous Artesunate | 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 mg/kg Intravenous Artesunate | 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 |
| 4 mg/kg Intravenous Artesunate | 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 |
| 4 mg/kg Intravenous Artesunate | 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 |
| 4 mg/kg Intravenous Artesunate | 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 |
| 4 mg/kg Intravenous Artesunate | Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion | Heart Rate change of at least 15bpm | Increase | 6 Participants |
| 4 mg/kg Intravenous Artesunate | 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 | 1 Participants |
| 4 mg/kg Intravenous Artesunate | 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 | 6 Participants |
| 8 mg/kg Intravenous Artesunate | 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 | 4 Participants |
| 8 mg/kg Intravenous Artesunate | 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 |
| 8 mg/kg Intravenous Artesunate | 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 |
| 8 mg/kg Intravenous Artesunate | 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 | 6 Participants |
| 8 mg/kg Intravenous Artesunate | Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion | Heart Rate change of at least 15bpm | Increase | 3 Participants |
| 8 mg/kg Intravenous Artesunate | 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 |
Secondary
Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL)
Cmax was calculated after single 2.0, 4.0 and 8.0 mg/kg dose of Artesunate daily for 3 days (ng/mL)
Time frame: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| 2 mg/kg Intravenous Artesunate | Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL) | Cmax 2 | 2923 ng/mL | Standard Deviation 1050 |
| 2 mg/kg Intravenous Artesunate | Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL) | Cmax 1 | 3015 ng/mL | Standard Deviation 882 |
| 2 mg/kg Intravenous Artesunate | Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL) | Cmax 3 | 2933 ng/mL | Standard Deviation 810 |
| 4 mg/kg Intravenous Artesunate | Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL) | Cmax 1 | 6057 ng/mL | Standard Deviation 2456 |
| 4 mg/kg Intravenous Artesunate | Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL) | Cmax 3 | 5762 ng/mL | Standard Deviation 3426 |
| 4 mg/kg Intravenous Artesunate | Cmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (ng/mL) | Cmax 2 | 5943 ng/mL | Standard Deviation 2110 |
Secondary
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)
For 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)
Time frame: Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| 2 mg/kg Intravenous Artesunate | 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) | 2421 ng*hr/mL | Standard Deviation 755 |
| 2 mg/kg Intravenous Artesunate | 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) | 2325 ng*hr/mL | Standard Deviation 721 |
| 2 mg/kg Intravenous Artesunate | 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) | 1746 ng*hr/mL | Standard Deviation 247 |
| 2 mg/kg Intravenous Artesunate | 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) | 1880 ng*hr/mL | Standard Deviation 795 |
| 2 mg/kg Intravenous Artesunate | 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) | 1636 ng*hr/mL | Standard Deviation 342 |
| 2 mg/kg Intravenous Artesunate | 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) | 1627 ng*hr/mL | Standard Deviation 957 |
| 2 mg/kg Intravenous Artesunate | 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) | 5683 ng*hr/mL | Standard Deviation 550 |
| 4 mg/kg Intravenous Artesunate | 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) | 5728 ng*hr/mL | Standard Deviation 1980 |
| 4 mg/kg Intravenous Artesunate | 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) | 5272 ng*hr/mL | Standard Deviation 2089 |
| 4 mg/kg Intravenous Artesunate | 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) | 14733 ng*hr/mL | Standard Deviation 5846 |
| 4 mg/kg Intravenous Artesunate | 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) | 4374 ng*hr/mL | Standard Deviation 2362 |
| 4 mg/kg Intravenous Artesunate | 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) | 4631 ng*hr/mL | Standard Deviation 2402 |
| 4 mg/kg Intravenous Artesunate | 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) | 4379 ng*hr/mL | Standard Deviation 2361 |
| 4 mg/kg Intravenous Artesunate | 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) | 5766 ng*hr/mL | Standard Deviation 2121 |
Secondary
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)
For the predicted concentration at the time of dose administration (C0) was determine for each dose (ng/mL)
Time frame: Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| 2 mg/kg Intravenous Artesunate | 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 | 17265 ng/mL | Standard Deviation 3590 |
| 2 mg/kg Intravenous Artesunate | 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 | 29056 ng/mL | Standard Deviation 12850 |
| 2 mg/kg Intravenous Artesunate | 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 | 23417 ng/mL | Standard Deviation 10200 |
| 4 mg/kg Intravenous Artesunate | 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 | 53503 ng/mL | Standard Deviation 33017 |
| 4 mg/kg Intravenous Artesunate | 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 | 54674 ng/mL | Standard Deviation 43261 |
| 4 mg/kg Intravenous Artesunate | 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 | 66380 ng/mL | Standard Deviation 32973 |
Secondary
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)
For 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.
Time frame: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| 2 mg/kg Intravenous Artesunate | 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 | 4065 ng*hr/mL | Standard Deviation 771 |
| 2 mg/kg Intravenous Artesunate | 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 | 4122 ng*hr/mL | Standard Deviation 809 |
| 2 mg/kg Intravenous Artesunate | 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 | 3509 ng*hr/mL | Standard Deviation 970 |
| 2 mg/kg Intravenous Artesunate | 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 | 3748 ng*hr/mL | Standard Deviation 646 |
| 2 mg/kg Intravenous Artesunate | 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 | 3394 ng*hr/mL | Standard Deviation 974 |
| 2 mg/kg Intravenous Artesunate | 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 | 3701 ng*hr/mL | Standard Deviation 647 |
| 2 mg/kg Intravenous Artesunate | 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 | 11379 ng*hr/mL | Standard Deviation 2128 |
| 4 mg/kg Intravenous Artesunate | 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 | 8011 ng*hr/mL | Standard Deviation 2780 |
| 4 mg/kg Intravenous Artesunate | 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 | 8122 ng*hr/mL | Standard Deviation 2750 |
| 4 mg/kg Intravenous Artesunate | 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 | 25685 ng*hr/mL | Standard Deviation 8715 |
| 4 mg/kg Intravenous Artesunate | 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 | 8405 ng*hr/mL | Standard Deviation 2715 |
| 4 mg/kg Intravenous Artesunate | 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 | 8842 ng*hr/mL | Standard Deviation 3265 |
| 4 mg/kg Intravenous Artesunate | 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 | 8571 ng*hr/mL | Standard Deviation 2817 |
| 4 mg/kg Intravenous Artesunate | 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 | 8992 ng*hr/mL | Standard Deviation 3355 |
Secondary
Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr)
Tmax was calculated after single 2.0, 4.0 and 8.0 mg/kg dose of Artesunate daily for 3 days (hr)
Time frame: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| 2 mg/kg Intravenous Artesunate | Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr) | Tmax 2 (hr) | 0.208 hr | Standard Deviation 0.137 |
| 2 mg/kg Intravenous Artesunate | Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr) | Tmax 1 (hr) | 0.208 hr | Standard Deviation 0.137 |
| 2 mg/kg Intravenous Artesunate | Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr) | Tmax 3 (hr) | 0.292 hr | Standard Deviation 0.102 |
| 4 mg/kg Intravenous Artesunate | Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr) | Tmax 1 (hr) | 0.208 hr | Standard Deviation 0.137 |
| 4 mg/kg Intravenous Artesunate | Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr) | Tmax 3 (hr) | 0.250 hr | Standard Deviation 0.129 |
| 4 mg/kg Intravenous Artesunate | Tmax Assessment After Single 2.0, 4.0 and 8.0 mg/kg Dose of Artesunate Daily for 3 Days (hr) | Tmax 2 (hr) | 0.181 hr | Standard Deviation 0.238 |