Study of the Safety of Intravenous Artesunate

NCT00292942 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: WRAIR 1142USUHS G183SPA-13419
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Malaria; Malaria, Cerebral

Keywords

artesunate; artemisinin; falciparum

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  up to 21 days

Secondary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

Study Arms (4)

2 mg/kg Intravenous Artesunate

EXPERIMENTAL

2 mg/kg of Intravenous artesunate

Drug: Intravenous Artesunate

4 mg/kg Intravenous Artesunate

EXPERIMENTAL

4 mg/kg of Intravenous artesunate

Drug: Intravenous Artesunate

8 mg/kg Intravenous Artesunate

EXPERIMENTAL

8 mg/kg of Intravenous artesunate

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.

Drug: Placebo

Interventions

Intravenous Artesunate DRUG

Three doses of Intravenous Artesunate drug at 2, 4, or 8 mg/kg in diluent Phosphate Buffer (0.3 M, pH 8.1)

Also known as: IV AS

2 mg/kg Intravenous Artesunate; 4 mg/kg Intravenous Artesunate; 8 mg/kg Intravenous Artesunate

Placebo DRUG

Mannitol (200 mg/vial) diluted in Phosphate Buffer and given IV in equivalent volume by subject's weight.

Also known as: Mannitol

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Uniformed Services University of the HEalth Sciences

Bethesda, Maryland, 20814-4799, United States

Location

MeSH Terms

Conditions

Malaria; Malaria, Cerebral

Interventions

Mannitol

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Central Nervous System Protozoal Infections; Central Nervous System Parasitic Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Louis Cantilena, Jr., MD, PhD
• Organization: Uniformed Services University of the Health Sciences

lcantilina@usuhs.mil

301-295-0016

Study Officials

• Peter J Weina, MD, PhD

  Walter Reed Army Institute of Research (WRAIR)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2006
• First Posted: February 16, 2006
• Study Start: June 12, 2006
• Primary Completion: January 17, 2007
• Study Completion: January 1, 2008
• Last Updated: October 25, 2018
• Results First Posted: October 25, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)