Phase I Trial of an Investigational Small Pox Medication

This was a Phase I, double-blind, cross-over, single-dose study of the orally administered anti-orthopoxvirus compound, ST-246, to 12 healthy, fed volunteers between the ages of 18 and 50 years. Subjects were randomized such that 6 subjects received either ST-246 Form I (monohydrate) followed 10 days later after a wash-out period by Form V (hemihydrate), and 6 subjects received ST-246 Form V followed by Form I, as for the previous group.

Both forms of ST-246 were similar in the way they were manufactured. 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.

Inclusion criteria

• 18 to 50 years
• Available for clinical follow-up duration of study.
• Able/willing to give written consent.
• Good general health; no clinically significant medical history.
• Refrain from taking any medications from screening through 72 hours after last dose.
• Adequate venous access.
• PE and lab results without clinically significant findings within 28 days prior to receipt of drug.
• Meet Lab Criteria within 28 days prior to receipt of drug.
• Negative pregnancy test
• Non smokers
• No alcohol or caffeine
• Participant or partner has undergone surgical sterilization, or the participant agrees either to be abstinent or use two non-hormonal methods of contraception for duration of the study

Exclusion criteria

• Marked baseline prolongation of QT/corrected QT interval (QTc) interval (
• History of additional risk factors for Torsade de Pointes
• Clinically significant abnormal ECG
• Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or prolongation of the PR interval
• Family history of Sudden Cardiac Death not clearly due to acute myocardial infarction.
• History of any clinically significant conditions including:

• Asthma
• Diabetes mellitus
• History of thyroidectomy or thyroid disease
• Serious angioedema episodes
• Head trauma resulting in a diagnosis of TBI other than concussion
• Seizure or history of seizure
• Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with intramuscular injections or blood draws
• Malignancy
• Family history of idiopathic seizures
• History or presence of neutropenia or other blood dyscrasia
• Known Hepatitis B or Hepatitis C infection
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome illness.
• Current or recent history of a clinically significant bacterial, fungal, or mycobacterial infection.
• Known clinically significant chronic viral infection (or current clinically significant viral infection
• History of frequent or severe headaches or migraines
• Known chronic bacterial, mycobacterial, fungal, parasitic, or protozoal infection
• Woman who is pregnant or is breast-feeding or planning to become pregnant
• On any concomitant medications
• History of drug allergy that, in the opinion of the PI, contraindicates participation in the trial.
• Inability to swallow medication
• Body Mass Index above 35 or below 18,
• Current drug abuse or alcohol abuse.
• 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
• Clinically significant lactose intolerance
• Received experimental drug within 30 days
• Vaccination within 30 days
• Total of more than 350 milliliters (mL) of blood drawn in 2 months
• Treatment with any immunosuppressant or immunomodulatory medication in 3 months
• Any condition 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
• History or diagnosis that would affect absorption of study medication