SIGA-246 to Treat Smallpox
This study will test an experimental antiviral drug called SIGA-246 for use against the smallpox virus (variola). Although smallpox has been universally eradicated, it could possibly be brought back as a bioweapon. In the event of a smallpox attack, it would be best to have an antiviral medication in addition to the smallpox vaccine. SIGA-246 has shown to have activity against other viruses from the same family (orthopoxvirus) that smallpox belongs to.
Healthy volunteers who are 18-50 years of age and are not pregnant or breastfeeding may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, and an electrocardiogram.
Participants are randomly assigned to receive a one-time dose of SIGA-246 (either 500 mg, 1000 mg, or 2000 mg) or a placebo (sugar pill) taken by mouth. They report to the clinic in the morning for the following procedures:
- Insertion of intravenous (IV) line in the forearm.
- Blood and urine tests before taking the study drug.
- Drug administration within 30 minutes of eating a light breakfast.
- Blood sampling from the IV line at 30 minutes and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5 and 6, 10 and 12 hours after taking SIGA-246 to determine how the drug is absorbed, distributed, broken down and excreted. Samples are also collected by needle stick at 24 and 48 hours for the same tests.
- Electrocardiogram at 2 hours and 24 hours after taking SIGA-246.
- 24-hour urine collection after taking the SIGA-246.
- Complete diary card at home for 7 days after taking the SIGA-246.
- Follow-up visits at about 2 weeks and about 4 weeks after taking SIGA-246.
- Checks for health changes or problems at every visit.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Double-Blind, Randomized, Placebo-Controlled, Ascending Single-Dose, Phase I Trial of the Anti-Orthopoxvirus Compound SIGA-246 in Healthy Volunteers|
|Study Start Date:||March 2006|
|Estimated Study Completion Date:||August 2006|
Historically, smallpox has been responsible for hundreds of millions of deaths. In 1980 the World Health Organization declared the global eradication of smallpox which was achieved through a surveillance and vaccination program using live virus vaccine. In spite of its eradication, the deliberate use of smallpox as a bioterrorist agent remains a threat. While there is an effective vaccine, there have been concerns regarding vaccine complications which have prevented universal vaccination in the absence of disease exposure. In addition, in the event of a smallpox outbreak vaccination may be ineffective in immunocompromised individuals and in those who were exposed to the virus more than 3 days prior to vaccination. Antiviral therapy may be able to supplement a vaccine, however, there are limitations of the currently available drug options. SIGA-246 is an oral medication that has been shown to be highly active against variola virus and has demonstrated safety in animal models. The primary objective of this study is to assess the safety and tolerability of SIGA-246 at various doses with a secondary objective of evaluating the pharmacokinetics of the drug. To achieve these objectives, 30 healthy volunteers will be enrolled into one of three dosing groups (500 mg, 1000 mg, or 2000 mg) to receive an oral, single dose of SIGA-246 or placebo. In each of the three ascending dosing groups there will be 8 active drug recipients and 2 placebo recipients. Safety of the study agents will be assessed by history, physical, and laboratory evaluations. Pharmacokinetic endpoints include C(max), T(max), t(1/2), AUC, CI and urinary excretion. Urine will be collected in 3 8-hour intervals and serial blood samples will be obtained after study agent administration.
|United States, Maryland|
|National Institute of Allergy and Infectious Diseases (NIAID)|
|Bethesda, Maryland, United States, 20892|