Phase I Trial of an Investigational Small Pox Medication

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
SIGA Technologies
ClinicalTrials.gov Identifier:
NCT00728689
First received: August 1, 2008
Last updated: September 15, 2010
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Orthopoxviral Disease
Smallpox
Monkey Pox
Other: Days 1 - 3
Other: Days 11 - 13
Phase 1

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

Resource links provided by NLM:


Further study details as provided by SIGA Technologies:

Primary Outcome Measures:
  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: t½ [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ] [ Designated as safety issue: No ]
    Mean terminal half-life (t½; hrs) for Forms I and V were calculated from [plasma] vs time profiles.

  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-τ [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ] [ Designated as safety issue: No ]
    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-τ; ng*hr/mL).

  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-∞ [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ] [ Designated as safety issue: No ]
    Area under the drug concentration-time curve from time zero to infinity (AUC0-∞; ng*hr/mL).

  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Cmax [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ] [ Designated as safety issue: No ]
    Maximum drug concentration in plasma, determined directly from individual concentration-time data (Cmax)

  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Tmax [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration(Tmax; hrs) for Forms I and V were calculated from [plasma] vs time profiles.


Secondary Outcome Measures:
  • 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 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

    Evaluated safety parameters included:

    1. physical examination/vital signs
    2. electrocardiograms (heart rate, PR interval, QRS duration, QT interval, and QTc Bazett)
    3. laboratory safety tests (hematology, chemistry, urinalysis)
    4. 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.


Enrollment: 12
Study Start Date: August 2008
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group ST-246 Form I (followed by Form V)
Each of six subjects receive a single 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 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.
Other: 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).
Other Name: Tecovirimat
Other: 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.
Other Name: Tecovirimat
Active Comparator: Group ST-246 Form V (followed by Form I)
Each of six subjects receive a single 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 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.
Other: 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).
Other Name: Tecovirimat
Other: 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.
Other Name: Tecovirimat

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00728689

Locations
United States, Florida
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
Sponsors and Collaborators
SIGA Technologies
Investigators
Principal Investigator: Thomas C Marbury, MD Orlando Clinical Research Center
  More Information

No publications provided

Responsible Party: Dennis Hruby, SIGA Technologies, Inc.
ClinicalTrials.gov Identifier: NCT00728689     History of Changes
Other Study ID Numbers: SIGA-246-005, DMID 08-0014
Study First Received: August 1, 2008
Results First Received: June 10, 2009
Last Updated: September 15, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by SIGA Technologies:
Orthopoxviral
Smallpox
Monkey pox

Additional relevant MeSH terms:
Smallpox
Monkeypox
Poxviridae Infections
DNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on September 16, 2014