Safety, Tolerability and Pharmacokinetics of TPOXX When Administered Orally for 28 Days

Inclusion Criteria

• Subject is male or female between 18 and 80 years of age, inclusive.
• Subject is available for clinical follow-up for the duration of the study.
• Women of childbearing potential have a negative beta human chorionic gonadotropin pregnancy test (serum) at the screening visit and a confirmatory negative pregnancy test on Day 1 or Day -1 (PK subset) before receipt of study drug, and meet one of the following criteria:
• Subject or their partner has undergone surgical sterilization.
• Subject is postmenopausal, defined as 12 consecutive months with no menses without an alternative medical cause and has a documented plasma follicle stimulating hormone level >40 IU/mL.
• Subject agrees to be abstinent (ie, heterosexually inactive) for the duration of the study.
• Subject agrees to consistently use 1 of the following methods of contraception from the beginning of screening (which they had been consistently using for at least 30 days before the first dose of study drug) through 30 days after the last dose of study drug:

i. Condoms, male or female, with a spermicide NOTE: For male subjects, condoms must be used for 90 days after the last dose of study drug. Male and female condoms should not be used together, as this can reduce their effectiveness.

ii. Diaphragm or cervical cap with spermicide iii. Intrauterine device with spermicide iv. Oral contraceptives or other hormonal methods NOTE: Another nonhormonal method of contraception must be used in conjunction with oral contraceptives.

v. Male sexual partner who had undergone a vasectomy at least 3 months before screening

• Male subjects must agree to not donate sperm from the first dose of study drug through 90 days after the last dose of study drug.
• Subject is considered by the investigator to be in good general health as determined by medical history (no hospitalizations for chronic medical conditions in the previous 2 years), clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening.
• Subject agrees not to use nicotine products, including electronic vapor cigarettes, nicotine patches, or nicotine gum, for at least 30 days before the Day 1 randomization visit through completion of the Day 29 dosing complete/early termination (ET) visit.
• Subject agrees to comply with the study dietary requirements throughout the study drug dosing period.
• Subject agrees not to consume caffeine- or xanthine-containing products during all study visits, including overnight stays (PK subset); sodas, coffee, and tea designated as caffeine free or noncaffeinated may be consumed on study days; caffeine may be consumed while at home and between study visits.
• Subject agrees to comply with all protocol requirements.
• Subject has adequate venous access if participating in the PK subset.
• Subject is able and willing to provide written informed consent.

Exclusion Criteria

• Subject is a female who is pregnant or breastfeeding or planning to become pregnant within 3 months after the last dose of study drug.
• Subject has a history of any clinically significant conditions including:
• Asthma treated with oral systemic steroids within the past 6 months
• Diabetes mellitus (type 1 or 2), with the exception of gestational diabetes
• Hypertension that is poorly controlled (repeat readings >140 mm Hg systolic and/or >90 mmHg diastolic)
• Thyroidectomy or thyroid disease that required medication within the past 12 months
• Serious angioedema episodes within the previous 3 years or requiring medication in the previous 2 years
• History of head trauma resulting in a diagnosis of traumatic brain injury other than concussion
• Frequent episodes of headache
• Subject has received any vaccination within 28 days prior to Day 1 or plans to receive a vaccination at any time during the treatment period or within 28 days after study Day 28.
• Subject has received treatment in another clinical study of a