SIGA-246 to Treat Smallpox

• INCLUSION CRITERIA:

A participant must meet all of the following criteria:

1. 18 to 50 years old, inclusive.
2. Available for clinical follow-up for the duration of the study.
3. Able and willing to give written informed consent.
4. In good general health without clinically significant medical history.
5. Be able to refrain from taking any medications for 48 hours after study agent administration.
6. Have adequate venous access.

7. Physical examination and laboratory results without clinically significant findings within the 28 days prior to receipt of study drug (i.e., satisfactorily completed screening).

   Laboratory criteria within 28 days prior to receipt of study drug:

8. Hemoglobin within institutional normal range.
9. WBC within institutional normal range.
10. Absolute neutrophil count (ANC) within institutional normal range.
11. Total lymphocyte count within institutional normal range.
12. Platelets within institutional normal range.
13. ALT (SGPT) within institutional norm range. If the ALT is not within normal limits, it may be repeated once within the 28 days prior to receipt of the study drug.
14. Serum creatinine within institutional normal range.
15. Normal urinalysis defined as negative glucose, negative or trace protein, and negative or trace blood in the urine.
16. Negative beta-HCG pregnancy test (urine or serum) on day of receipt of study drug for women of childbearing potential.

17. The participant or his or her partner has undergone surgical sterlization, or the participant agrees either to be abstinent (i.e., heterosexually inactive) or to consistently use two of the following non-hormonal methods of contraception within the 21 days prior to receipt of the study drug and throughout the duration of the study:

    • Condoms, male or female, with or without a spermicide;
    • diaphragm or cervical cap with spermicide;
    • intrauterine device.

EXCLUSION CRITERIA:

A volunteer will be excluded if one or more of the following conditions apply:

1. Woman who is breast-feeding or planning to become pregnant prior to or during the 4 weeks of study participation.

2. Volunteer is on any concomitant medications, including over the counter medications or herbal supplements, for 14 days before the administration of the study agent.

   Volunteer has a history of any clinically significant conditions including:

3. Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or intravenous corticosteroids.
4. Diabetes mellitus (type I or II), with the exception of gestational diabetes.
5. History of thyroidectomy or thyroid disease that required medication within the past 12 months.
6. Serious angioedema episodes within the previous three years or requiring medication in the previous two years.
7. Hypertension requiring medication.
8. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.
9. Malignancy that is active, or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study.

10. Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not requiring treatment within the last 3 years.

    Volunteer has:

11. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
12. Inability to swallow study medication.
13. Any clinically significant abnormal electrocardiogram findings as determined by the cardiologist in the context of the volunteer's history.
14. Received experimental drug within 30 days of study entry or will participate in any experimental study during the study period.
15. Active illicit drug or alcohol abuse.
16. Any clinically significant lactose intolerance that according to the clinician would be unacceptable for study participation, e.g. lactose intolerance that requires Lactaid or other OTC medications to prevent or alleviate symptoms.