MalariaPhase 1NCT00292942
Study of the Safety of Intravenous Artesunate
A Phase 1 study testing Intravenous Artesunate in people with Malaria and Malaria, Cerebral, run by U.S. Army Medical Research and Development Command at 1 site in United States.
Trial summary
The purpose of this study is to establish the safety, tolerability, and pharmacokinetics of a multiple dose of the antimalarial drug artesunate. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Malaria, Cerebral
- What is being tested?
- Intravenous Artesunate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2006to Jan 2008
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Uniformed Services University of the HEalth Sciences
Bethesda, Maryland, 20814-4799
About this study
Official title: A Phase 1 Double-Blind, Placebo-Controlled, Randomized Multiple Dose Escalation Study to Evaluate the Safety, Tolerance, and Pharmacokinetics/Pharmacodynamics of a New GMP Formulation of Intravenous Artesunate if Healthy Subjects
The purpose of this study is to establish the safety, tolerability, and pharmacokinetics of a multiple dose of the antimalarial drug artesunate.
Read the 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.
- Conditions
- Malaria, Malaria, Cerebral
- Being tested
- Intravenous Artesunate, Placebo
- Keywords
- artesunate, artemisinin, falciparum
- Medical subject headings
- Malaria, Malaria, Cerebral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous ArtesunateDrug
Also called IV AS
Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)
PlaceboDrug
Also called Mannitol
Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
| Study group | Role | What they receive |
|---|---|---|
| 2 mg/kg Intravenous Artesunate | Experimental | 2 mg/kg of Intravenous artesunate Receives: Drug: Intravenous Artesunate |
| 4 mg/kg Intravenous Artesunate | Experimental | 4 mg/kg of Intravenous artesunate Receives: Drug: Intravenous Artesunate |
| 8 mg/kg Intravenous Artesunate | Experimental | 8 mg/kg of Intravenous artesunate Receives: Drug: Intravenous Artesunate |
| Placebo | Placebo comparator | Mannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 21 days
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
Measured: up to 21 days
Secondary outcomes (6)
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
Measured: screening, on Day -1, on Days 1, 2, and 3, and at each follow-up visit
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)
Measured: Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusion
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)
Measured: Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusion
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.
Measured: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion
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)
Measured: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion
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)
Measured: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2006 (estimated)
- Study start12 Jun 2006
- Primary completion17 Jan 2007
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- Walter Reed Army Institute of Research (WRAIR)
- Responsible party
- Sponsor
- Investigators
- Peter J Weina, MD, PhD, Study director, Walter Reed Army Institute of Research (WRAIR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00292942
- Sponsor's protocol ID
- WRAIR 1142
- Other IDs
- USUHS G183SP, A-13419
- Status last verified
- Feb 2018
- First submitted
- 14 Feb 2006
- Last updated
- 25 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: WRAIR
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Double-Blind, Placebo-Controlled, Randomized Multiple Dose Escalation Study to Evaluate the Safety, Tolerance, and Pharmacokinetics/Pharmacodynamics of a New GMP Formulation of Intravenous Artesunate if Healthy Subjects
- ClinicalTrials.gov ID
- NCT00292942
- Acronym / sponsor ID
- WRAIR 1142
- Conditions
- Malaria, Malaria, Cerebral
- Keywords
- artesunate, artemisinin, falciparum
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- Walter Reed Army Institute of Research (WRAIR)
- Study start
- 12 Jun 2006 (actual)
- Primary completion
- 17 Jan 2007 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 16 Feb 2006 (estimated)
- Results
- Posted 25 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 2 mg/kg Intravenous Artesunate | Experimental | Drug: Intravenous Artesunate2 mg/kg of Intravenous artesunate |
| 4 mg/kg Intravenous Artesunate | Experimental | Drug: Intravenous Artesunate4 mg/kg of Intravenous artesunate |
| 8 mg/kg Intravenous Artesunate | Experimental | Drug: Intravenous Artesunate8 mg/kg of Intravenous artesunate |
| Placebo | Placebo comparator | Drug: PlaceboMannitol (200 mg/vial) diluted in phosphate buffer and delivered in an equivalent volume by subject's weight as artesunate. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous ArtesunateAlso: IV ASThree doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1) | Drug | 2 mg/kg Intravenous Artesunate, 4 mg/kg Intravenous Artesunate, 8 mg/kg Intravenous Artesunate |
| PlaceboAlso: MannitolMannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight. | Drug | Placebo |
Primary outcome
Number of Participants With AEs
Time frame: 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
Time frame: 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
6 secondary outcomes
Cardiovascular Responses: Number of Participants With Changes in Blood Pressure and Heart Rate After Infusion
Time frame: screening, on Day -1, on Days 1, 2, and 3, and at each follow-up visit
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)
Time frame: Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusion
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)
Time frame: Pre-dose, 5, 20, 40 minutes after infusion and 1, 2, 4, 8, 24 and 72 hours after infusion
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)
Time frame: Pre-dose, 5, 20, 40 minutes after infution and 1, 2, 4, 8, 24 and 72 hours after infusion
Cmax Assessment 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
Tmax Assessment 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. WRAIR
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter J Weina, MD, PhD study director
Walter Reed Army Institute of Research (WRAIR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intravenous Artesunate in people with Malaria and Malaria, Cerebral, run by U.S. Army Medical Research and Development Command at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With AEs (time frame: up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2018.