• The comparison of pharmacokinetic parameters of area under the curve (AUC) and Cmax of Form I and Form V of ST-246 400 mg (2 × 200 mg) in fed, healthy subjects as assessed through blood samples. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  

• To evaluate the safety and tolerability of Form I and Form V of ST-246 in fed, normal, and healthy subjects as assessed through physical examination, vital signs, electrocardiograms (ECG), laboratory tests, and adverse events (AEs). [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  

Small pox is a serious, contagious, and sometimes fatal infectious disease. There is no specific treatment for smallpox disease, and the only prevention is vaccination. The pox part of smallpox is derived from the Latin word for "spotted" and refers to the raised bumps that appear on the face and body of an infected person.

There are two clinical forms of smallpox. Variola major is the severe and most common form of smallpox, with a more common form of smallpox, with a more extensive rash and higher fever. There are four types of variola major smallpox: ordinary (the most frequent type, accounting for 90% or more of cases); modified (mild and occurring in previously vaccinated persons); flat; and hemorrhagic (both rare and very severe). Historically, variola major has an overall fatality rate of about 30%; however flat and hemorrhagic smallpox usually are fatal. Variola minor is a less common presentation of smallpox, and a much less severe disease, with death rates historically of 1% or less.

This study will evaluate whether the body absorbs two different forms of ST-246® in the same manner and will also evaluate the safety and tolerability of ST-246®. All forms of ST-246® are similar in the way they are made. The only difference between Form I and Form V may be related to how it dissolves, and this may affect the way that it is absorbed in the human body. Information about any side effects that may occur will also be collected in this study.

It is planned that about 12 healthy men and women between the ages of 18 and 50 years old will be in this study.

Inclusion 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 from screening through 72 hours after the last dose of 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).

8. Laboratory Criteria within 28 days prior to receipt of study drug:

   Hemoglobin within institutional normal range White blood cells (WBC) within institutional normal range Absolute neutrophil count (ANC) within institutional normal range Total lymphocyte count within institutional normal range Platelets within institutional normal range Alanine aminotransferase (ALT; same as serum glutamate pyruvate transaminase [SGPT]) lower than or equal to the upper limit of normal of the laboratory institutional normal range Aspartate aminotransferase (AST; same as serum glutamic oxaloacetic transaminase [SGOT]) lower than or equal to the upper limit of normal of the laboratory institutional normal range Alkaline phosphatase lower than or equal to the upper limit of normal of the laboratory institutional normal range Serum creatinine lower than or equal to the upper limit of normal of the laboratory institutional normal range Normal urinalysis defined as negative glucose, negative or trace protein (less than 30 milligrams per deciliter), and negative or trace blood in the urine (less than 3 red cells per high power field)

9. Negative beta human chorionic gonadotropin pregnancy test (urine or serum) at screening and during baseline procedures prior to Treatment 1 and Treatment 2 for women of childbearing potential
10. Non smokers (including chewing tobacco). Subjects who have not used nicotine in any form for at least 2 months prior to screening and who will not use it until they have completed the study
11. Subjects who do not use alcohol or caffeine or who can abstain from their use from one week prior to study drug administration through completion of all study procedures.

12. The participant or his or her partner has undergone surgical sterilization, 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 screening period prior to receipt of the study drug and throughout the duration of the study:

    • Abstain, or

    • Use on of the following pairs of non-hormonal methods of contraception:

      i. Condoms, male or female, with spermicide ii. Diaphragm or cervical cap with spermicide iii. Intrauterine device with spermicide NOTE: The subject is to be withdrawn from the study if the urine pregnancy test is positive. A female subject who becomes pregnant during participation must be promptly withdrawn from the trial. She will be asked for consent to allow her treating physicians to provide the Sponsor or its designee with any follow-up information regarding the pregnancy and its outcome.

Exclusion Criteria:

1. A marked baseline prolongation of QT/corrected QT interval (QTc) interval (pre-dose QTcFridericia (QTcF) interval > 440 msec).
2. A history of additional risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
3. A clinically significant abnormal ECG as determined by the Principal Investigator (PI) that suggests previous myocardial infarction, acute ischemia, an arrhythmia or conduction defect.
4. Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or prolongation of the PR interval beyond 0.20 second
5. Family history of Sudden Cardiac Death not clearly due to acute myocardial infarction.

6. Subject has a history of any clinically significant conditions including:

   • Asthma
   • Diabetes mellitus (type I or II), with the exception of gestational diabetes.
   • History of thyroidectomy or thyroid disease that required medication within the past 12 months
   • Serious angioedema episodes within the previous three years or requiring medication in the previous two years
   • Head trauma resulting in a diagnosis of traumatic brain injury other than concussion
   • Seizure or history of seizure
   • Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular injections or blood draws
   • 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
7. Family history of idiopathic seizures
8. History or presence of neutropenia or other blood dyscrasia
9. Known Hepatitis B or Hepatitis C infection
10. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome illness. HIV positive regardless of CD4 count
11. Current or recent history (<30 days prior to screening and/or <45 days prior to randomization) of a clinically significant bacterial, fungal, or mycobacterial infection.
12. Known clinically significant chronic viral infection (e.g., human T-cell lymphotropic Virus I or II) or current clinically significant viral infection
13. Subject has a history of frequent or severe headaches or migraine headaches
14. Known chronic bacterial, mycobacterial, fungal, parasitic, or protozoal infection with the exception of clinically insignificant dermal infections
15. Woman who is pregnant or is breast-feeding or planning to become pregnant prior to or during the 8 weeks of study participation
16. Subject is on any concomitant medications, including over the counter medications or herbal supplements from screening to 72 hrs after the last administration of the study agent
17. History of drug allergy that, in the opinion of the PI, contraindicates participation in the trial. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled
18. Inability to swallow study medication
19. Body Mass Index above 35 or below 18, measured as weight corrected for height (weight in kg/[height in meters]2) or weight less than 110 lbs
20. Current drug abuse or alcohol abuse. Drug abuse screening will be performed for ethanol, amphetamines/metamphetamines, cannabinoids, cocaine, opiates, and barbiturates, and cotinine
21. Inability to refrain from physical exercise for a period of 24 hr before and after a PK day or refrain from consuming xanthines, grapefruit or grapefruit juice
22. Any clinically significant lactose intolerance
23. Received experimental drug within 30 days of study entry or will participate in any experimental study during the study period
24. Had any vaccination within 30 days prior to study entry
25. He/she has had a total of more than 350 milliliters (mL) of blood drawn for any reason during the 2 months prior to study drug administration (this does NOT include plasma donation)
26. Received treatment with any immunosuppressant or immunomodulatory medication within the 3 months prior to screening
27. Any medical, psychiatric, social condition (including homelessness), occupational reason or other responsibility that, in the judgment of the PI, would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol
28. He/she has a history or diagnosis that would affect absorption of the study medication (i.e., gastric bypass or similar surgery, short bowel syndrome, celiac disease, Crohn's disease)