Phase I Trial of an Investigational Small Pox Medication

SIGA Technologies

Status and phase: Completed; Phase 1

Conditions: Orthopoxviral Disease; Monkey Pox; Smallpox

Treatments: Drug: ST-246 Days 11 - 13; Drug: ST-246 Days 1 - 3

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00728689

SIGA-246-005

DMID 08-0014 (Other Identifier)

Details and patient eligibility

About

The purpose of this study was to evaluate the pharmacokinetic parameters and safety of a single dose of ST-246 400mg Form I versus ST-246 400mg Form V capsules in fed normal healthy volunteers.

Full description

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.

Enrollment: 12 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. 18 to 50 years
2. Available for clinical follow-up duration of study.
3. Able/willing to give written consent.
4. Good general health; no clinically significant medical history.
5. Refrain from taking any medications from screening through 72 hours after last dose.
6. Adequate venous access.
7. PE and lab results without clinically significant findings within 28 days prior to receipt of drug.
8. Meet Lab Criteria within 28 days prior to receipt of drug.
9. Negative pregnancy test
10. Non smokers
11. No alcohol or caffeine
12. 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

1. Marked baseline prolongation of QT/corrected QT interval (QTc) interval (

2. History of additional risk factors for Torsade de Pointes

3. Clinically significant abnormal ECG

4. Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or prolongation of the PR interval

5. Family history of Sudden Cardiac Death not clearly due to acute myocardial infarction.

6. 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

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.

11. Current or recent history of a clinically significant bacterial, fungal, or mycobacterial infection.

12. Known clinically significant chronic viral infection (or current clinically significant viral infection

13. History of frequent or severe headaches or migraines

14. Known chronic bacterial, mycobacterial, fungal, parasitic, or protozoal infection

15. Woman who is pregnant or is breast-feeding or planning to become pregnant

16. On any concomitant medications

17. History of drug allergy that, in the opinion of the PI, contraindicates participation in the trial.

18. Inability to swallow medication

19. Body Mass Index above 35 or below 18,

20. Current drug abuse or alcohol abuse.

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. Clinically significant lactose intolerance

23. Received experimental drug within 30 days

24. Vaccination within 30 days

25. Total of more than 350 milliliters (mL) of blood drawn in 2 months

26. Treatment with any immunosuppressant or immunomodulatory medication in 3 months

27. 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

28. History or diagnosis that would affect absorption of study medication

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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12 participants in 2 patient groups

Group ST-246 Form I (followed by Form V)

Active Comparator group

Description:

Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.

Treatment:

Drug: ST-246 Days 1 - 3

Drug: ST-246 Days 11 - 13

Group ST-246 Form V (followed by Form I)

Active Comparator group

Description:

Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.

Treatment:

Drug: ST-246 Days 1 - 3

Drug: ST-246 Days 11 - 13