Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetics of TPOXX When Administered Orally for 28 Days (NCT NCT04971109)

NCT ID: NCT04971109

Last Updated: 2024-12-27

Results Overview

Cmin - Minimum TPOXX concentration in plasma

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 467 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2024-12-27

Participant Flow

Participant milestones

Measure	TPOXX Treatment Group 1: At least one oral dose of 600 mg (3 × 200 mg capsules) TPOXX	TPOXX Placebo Treatment Group 2: At least one oral dose of placebo (3 capsules identical to TPOXX)
Overall Study STARTED	372	95
Overall Study COMPLETED	329	86
Overall Study NOT COMPLETED	43	9

Reasons for withdrawal

Measure	TPOXX Treatment Group 1: At least one oral dose of 600 mg (3 × 200 mg capsules) TPOXX	TPOXX Placebo Treatment Group 2: At least one oral dose of placebo (3 capsules identical to TPOXX)
Overall Study Adverse Event	4	3
Overall Study Failure to Meet Cont. Criteria	7	0
Overall Study Lost to Follow-up	8	2
Overall Study Physician Decision	5	0
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	18	3
Overall Study Subject was randomized in error	1	0

Baseline Characteristics

Safety, Tolerability and Pharmacokinetics of TPOXX When Administered Orally for 28 Days

Baseline characteristics by cohort

Measure	TPOXX n=369 Participants Treatment Group 1: An oral dose of 600 mg (3 × 200 mg capsules) TPOXX TPOXX: Study is based on Animal Regulatory Rule	TPOXX Placebo n=95 Participants Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX) TPOXX Placebo: Does not apply	Total n=464 Participants Total of all reporting groups
Age, Continuous	41.9 years STANDARD_DEVIATION 15.17 • n=5 Participants	41.7 years STANDARD_DEVIATION 15.48 • n=7 Participants	41.9 years STANDARD_DEVIATION 15.22 • n=5 Participants
Sex: Female, Male Female	222 Participants n=5 Participants	58 Participants n=7 Participants	280 Participants n=5 Participants
Sex: Female, Male Male	147 Participants n=5 Participants	37 Participants n=7 Participants	184 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	163 Participants n=5 Participants	43 Participants n=7 Participants	206 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	204 Participants n=5 Participants	52 Participants n=7 Participants	256 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	101 Participants n=5 Participants	28 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) White	249 Participants n=5 Participants	60 Participants n=7 Participants	309 Participants n=5 Participants
Race (NIH/OMB) More than one race	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Height (cm)	167.96 cm STANDARD_DEVIATION 10.070 • n=5 Participants	166.55 cm STANDARD_DEVIATION 11.061 • n=7 Participants	167.64 cm STANDARD_DEVIATION 10.283 • n=5 Participants
Weight (kg)	80.46 kg STANDARD_DEVIATION 16.684 • n=5 Participants	78.89 kg STANDARD_DEVIATION 16.724 • n=7 Participants	80.14 kg STANDARD_DEVIATION 16.686 • n=5 Participants
Body Mass Index (BMI)	28.41 Kilograms Per Square Meter STANDARD_DEVIATION 4.642 • n=5 Participants	28.41 Kilograms Per Square Meter STANDARD_DEVIATION 5.286 • n=7 Participants	28.41 Kilograms Per Square Meter STANDARD_DEVIATION 4.775 • n=5 Participants

PRIMARY outcome

Timeframe: 28 days

Cmin - Minimum TPOXX concentration in plasma

Outcome measures

Measure	TPOXX Pharmacokinetic Population Day 28 n=26 Participants Pharmacokinetic subset population administered TPOXX 600 mg BID for 28 days	TPOXX Placebo Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX) TPOXX Placebo: Does not apply
Cmin	792 ng/mL Geometric Coefficient of Variation 52.5	—

PRIMARY outcome

Timeframe: 28 days

Peak exposure when administered TPOXX

Outcome measures

Measure	TPOXX Pharmacokinetic Population Day 28 n=26 Participants Pharmacokinetic subset population administered TPOXX 600 mg BID for 28 days	TPOXX Placebo Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX) TPOXX Placebo: Does not apply
Cmax	1950 ng/mL Geometric Coefficient of Variation 45.1	—

PRIMARY outcome

Timeframe: 28 days

Total systematic exposure when administered TPOXX

Outcome measures

Measure	TPOXX Pharmacokinetic Population Day 28 n=26 Participants Pharmacokinetic subset population administered TPOXX 600 mg BID for 28 days	TPOXX Placebo Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX) TPOXX Placebo: Does not apply
AUC(0-last) - Total Systemic TPOXX Exposure	51100 ng*h/mL Geometric Coefficient of Variation 46.0	—

PRIMARY outcome

Timeframe: 28 days

Median hours post dose when administered TPOXX

Outcome measures

Measure	TPOXX Pharmacokinetic Population Day 28 n=26 Participants Pharmacokinetic subset population administered TPOXX 600 mg BID for 28 days	TPOXX Placebo Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX) TPOXX Placebo: Does not apply
Time To Maximum TPOXX Exposure	4 hours Interval 2.0 to 8.0	—

SECONDARY outcome

Timeframe: 58 Days

Number of participants with adverse events (Threshold: >/=2%)

Outcome measures

Measure	TPOXX Pharmacokinetic Population Day 28 n=369 Participants Pharmacokinetic subset population administered TPOXX 600 mg BID for 28 days	TPOXX Placebo n=95 Participants Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX) TPOXX Placebo: Does not apply
Adverse Events	90 participants	20 participants

Adverse Events

TPOXX

Serious events: 1 serious events

Other events: 90 other events

Deaths: 0 deaths

TPOXX Placebo

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	TPOXX n=369 participants at risk Treatment Group 1: An oral dose of 600 mg (3 x 200 mg capsules)TPOXX TPOXX: Study is based on Animal Regulatory Rule	TPOXX Placebo n=95 participants at risk Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX) TPOXX Placebo: Does not apply
Infections and infestations Dengue fever	0.00% 0/369 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	1.1% 1/95 • Number of events 1 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.27% 1/369 • Number of events 1 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	0.00% 0/95 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.

Other adverse events

Measure	TPOXX n=369 participants at risk Treatment Group 1: An oral dose of 600 mg (3 x 200 mg capsules)TPOXX TPOXX: Study is based on Animal Regulatory Rule	TPOXX Placebo n=95 participants at risk Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX) TPOXX Placebo: Does not apply
Gastrointestinal disorders Nausea	6.8% 25/369 • Number of events 28 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	4.2% 4/95 • Number of events 4 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.
Gastrointestinal disorders Diarrhoea	4.9% 18/369 • Number of events 20 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	2.1% 2/95 • Number of events 2 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.
Gastrointestinal disorders Vomiting	2.2% 8/369 • Number of events 8 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	2.1% 2/95 • Number of events 2 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.
Nervous system disorders Headache	8.4% 31/369 • Number of events 44 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	4.2% 4/95 • Number of events 4 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.
Infections and infestations Upper respiratory tract infection	1.1% 4/369 • Number of events 4 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	2.1% 2/95 • Number of events 2 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.
Investigations Alanine aminotransferase increased	0.27% 1/369 • Number of events 1 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	2.1% 2/95 • Number of events 2 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.
General disorders Fatigue	0.81% 3/369 • Number of events 3 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	2.1% 2/95 • Number of events 2 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/369 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.	2.1% 2/95 • Number of events 2 • Adverse event data was collected from Day 1 though the Day 58 follow-up telephone call. All AEs were followed until stable or until resolution as determined by the investigator and/or medical monitor. All-Cause Mortality was not assessed.

Additional Information

Emily Blum, Director of Clinical Development

SIGA Technologies

Phone: 541-224-1305

Email: eblum@siga.com

Results disclosure agreements

• Principal investigator is a sponsor employee The agreement restricts the right of the PI to discuss or publish trial results.
• Publication restrictions are in place

Restriction type: OTHER