Safety, Tolerability and PK of TPOXX in Adults Weighing More Than 120 KG

NCT04392739 | Completed Phase 4 Results FDA Drug

• 1 other identifier: SIGA-246-022
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Safety and PK study in adults weighing more than 120 kg

Conditions

Smallpox

Outcome Measures

Primary Outcomes (9)

• AUC0-t

  Area under the plasma concentration vs. time curve (AUC) from time 0 to the last quantifiable measurement following Day 7 dose administration. Samples were collected before the AM dose (0 hour), at 0.5, 1, 2, 4, 6, 8, 12 (before the PM dose), 14, 16, 18, 20, and 24 hours (Day 8, 24 hours after the AM dose on Day 7), and on Day 9 (48 hours after the AM dose on Day 7).

  Before the AM dose (0 hour), at 0.5, 1, 2, 4, 6, 8, 12 (before the PM dose), 14, 16, 18, 20, and 24 hours (Day 8, 24 hours after the AM dose on Day 7), and on Day 9 (48 hours after the AM dose on Day 7).

• AUC0-24

  Area under the plasma concentration vs. time curve (AUC) from time 0 to the 24-hour time-point following Day 7 dose administration. Samples were collected before the AM dose (0 hour), at 0.5, 1, 2, 4, 6, 8, 12 (before the PM dose), 14, 16, 18, 20, and 24 hours (Day 8, 24 hours after the AM dose on Day 7).

  Before the AM dose (0 hour), at 0.5, 1, 2, 4, 6, 8, 12 (before the PM dose), 14, 16, 18, 20, and 24 hours (Day 8, 24 hours after the AM dose on Day 7)

• AUC0-inf

  AUC from time 0 extrapolated to infinity

  Day 7

• Cmax

  Maximum observed plasma drug concentration. Samples were collected before the AM dose (0 hour), at 0.5, 1, 2, 4, 6, 8, 12 (before the PM dose), 14, 16, 18, 20, and 24 hours (Day 8, 24 hours after the AM dose on Day 7), and on Day 9 (48 hours after the AM dose on Day 7). The median time to achieve Cmax was 4 hours post-dose.

  Before the AM dose (0 hour), at 0.5, 1, 2, 4, 6, 8, 12 (before the PM dose), 14, 16, 18, 20, and 24 hours (Day 8, 24 hours after the AM dose on Day 7), and on Day 9 (48 hours after the AM dose on Day 7).

• Tmax

  Time to reach Cmax

  Day 7

• t1/2

  Terminal elimination half-life

  Day 7

• CL/F

  Apparent total body clearance

  Day 7

• Vd/F

  Apparent volume of distribution

  Day 7

• Ctrough

  Concentration observed prior to the next dose administration

  Day 7

Secondary Outcomes (16)

• AEs as Assessed by CTCAE

  30 days

• Subjects With at Least 1 AEs

  30 days

• Average Hemoglobin Concentration at Various Time Points; Mean (Standard Deviation)

  Baseline prior to dosing, 3 days post dose, 7 days post dose and 8 days post dose

• Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)

  Average Serum Chemistry at Baseline, 3 days post dose, 7 days post dose, and 8 days post dose

• Average Urinalysis pH Values at Various Time Points:Day 9; Mean (Standard Deviation)

  8 days post dose

Study Arms (1)

TPOXX

OTHER

TPOXX 600 mg BID x 7 days

Drug: Tpoxx

Interventions

Tpoxx DRUG

oral antiviral

TPOXX

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is male or female between 18 and 50 years of age, inclusive.
• Subject has a body weight \>120 kg at screening, at check-in on Day -1, and prior to dosing on Day 1.
• Women of childbearing potential, have a negative β human chorionic gonadotropin pregnancy test (serum) at the screening visit and a confirmatory negative serum pregnancy test on Day -1 before receipt of study drug, and meet 1 of the following criteria:
• The subject or their partner has undergone surgical sterilization
• The 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
• The subject agrees to be abstinent (ie, heterosexually inactive or women in a religious order)
• The 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.
• ii. Diaphragm or cervical cap with spermicide
• iii. Intrauterine device with spermicide
• iv. Oral contraceptives or other hormonal methods NOTE: Subject must agree to use an additional nonhormonal method of contraception 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 results, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings at screening.
• Subject agrees to comply with all protocol requirements.

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• 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
• 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
• Head trauma resulting in a diagnosis of traumatic brain injury other than concussion
• Frequent episodes of headache.
• Subject has received treatment in another clinical study of an investigational drug (or medical device) within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug.
• Subject has been previously enrolled in any clinical study involving TPOXX (tecovirimat).
• Subject has a history of relevant drug and/or food allergies (ie, allergy to tecovirimat or excipients, or any significant food allergy that could preclude a standard diet in the study site).
• Subject has any condition possibly affecting drug absorption (eg, previous surgery on the gastrointestinal tract, including removal of parts of the stomach, bowel, liver, gallbladder, or pancreas, with the exception of appendectomy).
• Subject has evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of the first dose of study drug), hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease. Exceptions to these criteria (eg, stable, mild joint disease unassociated with collagen vascular disease) may be made following discussions with the medical monitor.
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Sponsors & Collaborators

• SIGA Technologies: lead
• Biomedical Advanced Research and Development Authority: collaborator
• PPD Development, LP: collaborator

Study Sites (1)

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Smallpox

Interventions

tecovirimat

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Emily Blum, Assoc. Director of Clinical Research
• Organization: SIGA Technologies

eblum@siga.com

541-224-1305

Study Officials

• Dennis Hruby, PhD

  SIGA Chief Scientific Officer

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 19, 2020
• Study Start: July 19, 2019
• Primary Completion: December 5, 2019
• Study Completion: December 5, 2019
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)