Phase I Trial of an Investigational Small Pox Medication

NCT00728689 | Completed Phase 1 Results DMC

• 2 other identifiers: SIGA-246-005DMID 08-0014
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Orthopoxviral Disease; Smallpox; Monkey Pox

Keywords

Orthopoxviral; Smallpox; Monkey pox

Outcome Measures

Primary Outcomes (5)

• 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

• Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-τ

  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).

  Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs

• Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-∞

  Area under the drug concentration-time curve from time zero to infinity (AUC0-∞; ng\*hr/mL).

  Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs

• 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

• 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

Secondary Outcomes (1)

• 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

  4 weeks

Study Arms (2)

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

ACTIVE COMPARATOR

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.

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

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

ACTIVE COMPARATOR

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.

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

Interventions

ST-246 Days 1 - 3 DRUG

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).

Also known as: Tecovirimat

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

ST-246 Days 11 - 13 DRUG

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.

Also known as: Tecovirimat

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SIGA Technologies: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Ahmad S, Hasan H, Ahmad Suhaimi NA, Albakri KA, Abedalbaset Alzyoud A, Kadir R, Mohamud R. Comprehensive literature review of monkeypox. Emerg Microbes Infect. 2022 Dec;11(1):2600-2631. doi: 10.1080/22221751.2022.2132882.

  PMID: 36263798 DERIVED

MeSH Terms

Conditions

Smallpox; Mpox, Monkeypox

Interventions

tecovirimat

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Results Point of Contact

• Title: Annie Frimm, Vice President, Regulatory Affairs
• Organization: Siga Technologies, Inc.

afrimm@siga.com

951-303-8797

Study Officials

• Thomas C Marbury, MD

  Orlando Clinical Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2008
• First Posted: August 6, 2008
• Study Start: August 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: June 29, 2015
• Results First Posted: February 9, 2010

Record last verified: 2010-09

Locations

US (1)