Phase I Trial of an Investigational Small Pox Medication

Smallpox Clinical Trial

Official title:

A Phase I Randomized, Double-Blind, Crossover, Exploratory Study of the Pharmacokinetics of a Single Oral Dose of Form I Versus Form V Capsules of the Anti-Orthopoxvirus Compound ST-246® in Fed Normal Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00728689
• Other study ID #: SIGA-246-005
• Secondary ID: DMID 08-0014
• Status: Completed
• Phase: Phase 1
• First received: August 1, 2008
• Last updated: June 22, 2015
• Start date: August 2008
• Est. completion date: October 2008

Study information

• Verified date: September 2010
• Source: SIGA Technologies
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Monkey Pox
• Orthopoxviral Disease
• Smallpox

Intervention

Drug:
• ST-246 Days 1 - 3
First Intervention is on Days 1 - 3, and includes 6 patients dosed once orally with ST-246 Form I (Arm 1), and 6 patients dosed once orally with ST-246 Form V (Arm 2).
• ST-246 Days 11 - 13
Second Intervention is on Days 11 - 13 (after a 3 day post-treatment monitoring and 7 day wash-out period) where the 6 patients previously given ST-246 Form I (Arm 1) are now dosed once orally with ST-246 Form V, and the 6 patients previously given ST-246 Form V (Arm 2) are now dosed once orally with ST-246 Form I.

Locations

Country	Name	City	State
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
SIGA Technologies	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: t½	Mean terminal half-life (t½; hrs) for Forms I and V were calculated from [plasma] vs time profiles.	Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs	No
Primary	Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-t	Area under the drug concentration-time curve from time zero to time t, where t is the last timepoint with a drug concentration = lowest obtainable quantification (AUC0-t; ng*hr/mL).	Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs	No
Primary	Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-8	Area under the drug concentration-time curve from time zero to infinity (AUC0-8; ng*hr/mL).	Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs	No
Primary	Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Cmax	Maximum drug concentration in plasma, determined directly from individual concentration-time data (Cmax)	Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs	No
Primary	Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Tmax	Time to maximum plasma concentration(Tmax; hrs) for Forms I and V were calculated from [plasma] vs time profiles.	Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs	No
Secondary	Number of Study Participants Who Tolerated a Single Dose of ST-246 Form I vs. Form V as Determined by No Clinically Significant Changes in Safety Parameters	Evaluated safety parameters included: physical examination/vital signs; electrocardiograms (heart rate, PR interval, QRS duration, QT interval, and QTc Bazett); laboratory safety tests (hematology, chemistry, urinalysis); adverse events For a), b) and c), summary statistics (mean,SD, median, minm, maxm)for values, and changes from baseline(Day 1 pre-dose) to each timepoint, were measured and compared to laboratory normal reference ranges. Values for a)- d) were assigned grades according to DAIDS AE Grading Table. Any Grade of 3 or higher was considered severe and significant.	4 weeks	No