Study of the Safety of Intravenous Artesunate
Condition: Malaria; Malaria, Cerebral
MeSH terms: Malaria; Malaria, Cerebral
Intervention: Intravenous Artesunate; Placebo
Intervention description: Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1); Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.
Intervention MeSH terms: Artesunate; Mannitol
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: artesunate; artemisinin; falciparum

Summary:

      The purpose of this study is to establish the safety, tolerability, and pharmacokinetics of a
      multiple dose of the antimalarial drug artesunate.
    

Eligibility criteria:

        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