Trial Outcomes & Findings for Safety, Tolerability and PK of TPOXX in Adults Weighing More Than 120 KG (NCT NCT04392739)
NCT ID: NCT04392739
Last Updated: 2024-09-19
Results Overview
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).
COMPLETED
PHASE4
34 participants
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).
2024-09-19
Participant Flow
Participant milestones
| Measure |
TPOXX
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Overall Study
STARTED
|
34
|
|
Overall Study
COMPLETED
|
34
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability and PK of TPOXX in Adults Weighing More Than 120 KG
Baseline characteristics by cohort
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
34 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
34 Participants
n=5 Participants
|
|
Weight
|
138.13 kg
STANDARD_DEVIATION 20.881 • n=5 Participants
|
|
Height
|
176.40 cm
STANDARD_DEVIATION 9.649 • n=5 Participants
|
PRIMARY outcome
Timeframe: 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).Population: PK population
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).
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
AUC0-t
|
29500 ng*h/mL
Standard Error 26.0
|
PRIMARY outcome
Timeframe: 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)Population: PK population
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).
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
AUC0-24
|
20000 ng*h/mL
Standard Error 23.0
|
PRIMARY outcome
Timeframe: Day 7Population: PK population
AUC from time 0 extrapolated to infinity
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
AUC0-inf
|
33200 ng*h/mL
Standard Error 27.8
|
PRIMARY outcome
Timeframe: 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).Population: PK population
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.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Cmax
|
1350 ng/mL
Standard Error 29.0
|
PRIMARY outcome
Timeframe: Day 7Population: PK population
Time to reach Cmax
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Tmax
|
4.00 h
Interval 2.0 to 11.95
|
PRIMARY outcome
Timeframe: Day 7Population: PK population
Terminal elimination half-life
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
t1/2
|
12.9 h
Standard Error 19.3
|
PRIMARY outcome
Timeframe: Day 7Population: PK population
Apparent total body clearance
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
CL/F
|
64.8 L/h
Standard Error 26.0
|
PRIMARY outcome
Timeframe: Day 7Population: PK population
Apparent volume of distribution
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Vd/F
|
1180 L
Standard Error 29.9
|
PRIMARY outcome
Timeframe: Day 7Population: PK population
Concentration observed prior to the next dose administration
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Ctrough
|
617 ng/mL
Standard Error 35.6
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Safety population
Number of subjects with AEs as assessed by CTCAE
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
AEs as Assessed by CTCAE
|
12 participants
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Safety population
Number of subjects reported at least 1 adverse event
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Subjects With at Least 1 AEs
|
9 participants
|
SECONDARY outcome
Timeframe: Baseline prior to dosing, 3 days post dose, 7 days post dose and 8 days post dosePopulation: All subjects which were included in the safety population which is defined as all subjects who received at least one dose of TPOXX were included in this analysis.
Table 14.3.2.1.1Summary of Actual Value and Change from Baseline in Hematology Safety Population Summary tables of observed values and changes from baseline: for hematology laboratory tests with numeric values for subjects in the Safety Population; to each scheduled post-baseline and changes in low, normal, high, and abnormal were summarized comparing the results at each scheduled post-baseline visit.. Central laboratory reference ranges used for all clinical laboratory safety parameters
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average Hemoglobin Concentration at Various Time Points; Mean (Standard Deviation)
3 days post dose (Day 4)
|
142.6 Hemoglobin (g/L)
Standard Deviation 14.43
|
|
Average Hemoglobin Concentration at Various Time Points; Mean (Standard Deviation)
Baseline
|
138.0 Hemoglobin (g/L)
Standard Deviation 12.45
|
|
Average Hemoglobin Concentration at Various Time Points; Mean (Standard Deviation)
7 days post dose (Day 8)
|
142.0 Hemoglobin (g/L)
Standard Deviation 13.40
|
|
Average Hemoglobin Concentration at Various Time Points; Mean (Standard Deviation)
8 days post dose (Day 9)
|
140.6 Hemoglobin (g/L)
Standard Deviation 13.35
|
SECONDARY outcome
Timeframe: Average Serum Chemistry at Baseline, 3 days post dose, 7 days post dose, and 8 days post dosePopulation: All subjects which were included in the safety population which is defined as all subjects who received at least one dose of TPOXX were included in this analysis.
Table 14.3.2.2.1 Laboratory Results - Serum Chemistry Safety Population Summary tables of observed values and changes from baseline: for serum chemistry laboratory tests with numeric values for subjects in the Safety Population; to each scheduled post-baseline and changes in low, normal, high, and abnormal were summarized comparing the results at each scheduled post-baseline. Central laboratory reference ranges used for all clinical laboratory safety parameters
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Bilirubin (umol/L) Baseline
|
7.96 umol/L
Standard Deviation 3.339
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Urate (umol/L) 3 days post dose (Day 4)
|
406.0 umol/L
Standard Deviation 66.99
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Urate (umol/L) 7 days post dose (Day 8)
|
391.2 umol/L
Standard Deviation 65.17
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Urate (umol/L) 8 days post dose (Day 9)
|
391.5 umol/L
Standard Deviation 62.74
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Bilirubin (umol/L) 3 days post dose (Day 4)
|
10.24 umol/L
Standard Deviation 3.760
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Bilirubin (umol/L) 7 days post dose (Day 8)
|
10.25 umol/L
Standard Deviation 3.393
|
SECONDARY outcome
Timeframe: 8 days post dosePopulation: All subjects which were included in the safety population which is defined as all subjects who received at least one dose of TPOXX were included in this analysis.
Table 14.3.2.3.2 Laboratory Results - Urinalysis Safety Population Urinalysis laboratory tests with numeric values for subjects in the Safety Population; to each scheduled post-baseline and changes in low, normal, high, and abnormal were summarized comparing the results at each scheduled post-baseline visit. Central laboratory reference ranges used for all clinical laboratory safety parameters.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average Urinalysis pH Values at Various Time Points:Day 9; Mean (Standard Deviation)
|
5.93 pH
Standard Deviation 0.566
|
SECONDARY outcome
Timeframe: 9 daysPopulation: vital sign measurements values
Table 14.3.3.1.1 Vital Sign Results Safety Population Data listed shows the mean and standard deviation of systolic and diastolic blood pressure of 34 participants on day 9.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average Systolic and Diastolic Blood Pressures at 9 Day Time Point; Mean (Standard Deviation)
Systolic Blood Pressure (mmHg) 8 days post dose (Day 9)
|
122.9 mmHg
Standard Deviation 11.41
|
|
Average Systolic and Diastolic Blood Pressures at 9 Day Time Point; Mean (Standard Deviation)
Diastolic Blood Pressure (mmHg) 8 days post dose (Day 9)
|
67.1 mmHg
Standard Deviation 8.91
|
SECONDARY outcome
Timeframe: 9 daysPopulation: Mean Heart Rate after dosing.
Table 14.3.3.1.1 Vital Sign Results Safety Population Data listed shows the mean and standard deviation of heart rate of 34 participants on day 9.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average Heart Rate at 9 Day Time Point; Mean (Standard Deviation)
|
77.0 beats per minute
Standard Deviation 9.96
|
SECONDARY outcome
Timeframe: 9 daysPopulation: Mean Respiratory Rate after dosing.
Table 14.3.3.1.1 Vital Sign Results Safety Population Data listed shows the mean and standard deviation of respiratory rates for 34 participants on day 9.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average Respiratory Rate at 9 Day Time Point; Mean (Standard Deviation)
|
14.8 breaths per minute
Standard Deviation 2.15
|
SECONDARY outcome
Timeframe: 9 daysPopulation: Mean Body Temperature after dosing.
Table 14.3.3.1.1 Vital Sign Results Safety Population Data listed shows the mean and standard deviation of body temperatures for 34 participants on day 9.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average Body Temperature at 9 Day Time Point; Mean (Standard Deviation)
|
36.50 Celsius
Standard Deviation 0.281
|
SECONDARY outcome
Timeframe: 9 daysPopulation: Mean 12-lead ECG values after dosing.
Table 14.3.4.1.1 Electrocardiogram Results Safety Population Data listed shows the mean and standard deviation of 12 Lead EKG results for 34 participants on day 9.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average 12-lead ECG at 9 Day Time Point; Mean (Standard Deviation)
PR Interval, Aggregate (msec) 8 days post dose (Day 9)
|
171.1 msec
Standard Deviation 20.43
|
|
Average 12-lead ECG at 9 Day Time Point; Mean (Standard Deviation)
QRS Duration, Aggregate (msec) 8 days post dose (Day 9)
|
95.9 msec
Standard Deviation 10.38
|
SECONDARY outcome
Timeframe: 9 daysPopulation: Vital sign measurements, physical examination findings, and 12-lead ECG values after dosing.
Listing 16.2.8.8 Physical Exam Safety Population Subjects were collated based on review of system and classified by assessment as "normal", "abnormal" or "assessments not done" on day 9.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Normal: Skin
|
33 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: Skin
|
1 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Not Done: Skin
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Normal: HEENT
|
34 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: HEENT
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) HEENT: Not Done
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Normal: Pulmonary
|
34 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Not Done: Pulmonary
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Normal: Cardiovascular
|
34 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: Cardiovascular
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Not done: Cardiovascular
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abdomen: Normal
|
34 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: Abdomen
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Not Done: Abdomen
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Normal: Lymph Nodes
|
34 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: Neurological System
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Not Done: Neurological System
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Normal: Other
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: Pulmonary
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: Lymph Nodes
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Not Done: Lymph Nodes
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Normal: Musculoskeletal
|
33 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: Musculoskeletal
|
1 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Not Done: Musculoskeletal
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Normal: Neurological System
|
34 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Abnormal: Other
|
0 Participants
|
|
Physical Examination at Baseline Compared to Physical Examination 9 Days Post Dose
8 days post dose (Day 9) Not Done: Other
|
34 Participants
|
SECONDARY outcome
Timeframe: Day 1 pre dose, 3 days, 7 days, and 8 days post dosePopulation: All subjects which were included in the safety population which is defined as all subjects who received at least one dose of TPOXX were included in this analysis.
Table 14.3.2.2.1 Laboratory Results - Serum Chemistry Safety Population Summary tables of observed values and changes from baseline: for serum chemistry laboratory tests with numeric values for subjects in the Safety Population; to each scheduled post-baseline and changes in low, normal, high, and abnormal were summarized comparing the results at each scheduled post-baseline. Central laboratory reference ranges used for all clinical laboratory safety parameters
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Alk Phosphate (IU/L) Baseline
|
64.9 IU/L
Standard Deviation 20.51
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Aspartate Aminotransferase (IU/L) 3 days post dose (Day 4)
|
18.2 IU/L
Standard Deviation 5.69
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Gamma Glutamyl Transferase (IU/L) 8 days post dose (Day 9)
|
28.6 IU/L
Standard Deviation 13.01
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Lactate Dehydrogenase (IU/L) Baseline
|
159.2 IU/L
Standard Deviation 33.00
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Lactate Dehydrogenase (IU/L) 7 days post dose (Day 8)
|
142.9 IU/L
Standard Deviation 33.20
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Lactate Dehydrogenase (IU/L) 8 days post dose (Day 9)
|
148.1 IU/L
Standard Deviation 33.20
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Alanine Aminotransferase (IU/L) Baseline
|
21.8 IU/L
Standard Deviation 8.87
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Alanine Aminotransferase (IU/L) 3 days post dose (Day 4)
|
23.5 IU/L
Standard Deviation 11.84
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Alanine Aminotransferase (IU/L) 7 days post dose (Day 8)
|
25 IU/L
Standard Deviation 11.70
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Alanine Aminotransferase (I/UL) 8 days post dose (Day 9)
|
25.6 IU/L
Standard Deviation 12.21
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Alk Phosphate (IU/L)3 days post dose (Day 4)
|
61.0 IU/L
Standard Deviation 19.42
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Alk Phosphate (IU/L) 7 days post dose (Day 8)
|
66.9 IU/L
Standard Deviation 20.90
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Alk Phosphate (IU/L) 8 days post dose (Day 9)
|
67.4 IU/L
Standard Deviation 20.56
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Aspartate Aminotransferase (IU/L) Baseline
|
17.6 IU/L
Standard Deviation 4.63
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Aspartate Aminotransferase (IU/L) 7 days post dose (Day 8)
|
17.9 IU/L
Standard Deviation 4.49
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Aspartate Aminotransferase (IU/L) 8 days post dose (Day 9)
|
18.3 IU/L
Standard Deviation 4.46
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Gamma Glutamyl Transferase (IU/L) Baseline
|
27.4 IU/L
Standard Deviation 12.89
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Gamma Glutamyl Transferase (IU/L) 3 days post dose (Day 4)
|
27.6 IU/L
Standard Deviation 12.81
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Gamma Glutamyl Transferase (IU/L) 7 days post dose (Day 8)
|
28.6 IU/L
Standard Deviation 12.91
|
|
Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Various Time Points Mean (Standard Deviation)
Lactate Dehydrogenase (IU/L) 3 days post dose (Day 4)
|
147.8 IU/L
Standard Deviation 34.86
|
SECONDARY outcome
Timeframe: Day 1 pre dose, 3 days post dose, 7 days post dose and 8 days post dosePopulation: All subjects which were included in the safety population which is defined as all subjects who received at least one dose of TPOXX were included in this analysis.
Table 14.3.2.2.1 Laboratory Results - Serum Chemistry Safety Population Summary tables of observed values and changes from baseline: for serum chemistry laboratory tests with numeric values for subjects in the Safety Population; to each scheduled post-baseline and changes in low, normal, high, and abnormal were summarized comparing the results at each scheduled post-baseline. Central laboratory reference ranges used for all clinical laboratory safety parameters
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Albumin (g/L) Baseline
|
42.4 g/L
Standard Deviation 2.78
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Albumin (g/L) 3 days post dose (Day 4)
|
43.4 g/L
Standard Deviation 3.35
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Albumin (g/L) 7 days post dose (Day 8)
|
43.5 g/L
Standard Deviation 2.61
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Albumin (g/L)8 days post dose (Day 9)
|
44.2 g/L
Standard Deviation 2.73
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Globulin (g/L) Baseline
|
27.3 g/L
Standard Deviation 3.87
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Globulin (g/L) 3 days post dose (Day 4)
|
29.1 g/L
Standard Deviation 3.53
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Globulin (g/L) 7 days post dose (Day 8)
|
28.6 g/L
Standard Deviation 3.78
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Globulin (g/L) 8 days post dose (Day 9)
|
28.9 g/L
Standard Deviation 3.81
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Protein (g/L) Baseline
|
69.7 g/L
Standard Deviation 5.13
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Protein (g/L) 3 days post dose (Day 4)
|
72.4 g/L
Standard Deviation 5.16
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Protein (g/L) 7 days post dose (Day 8)
|
72.1 g/L
Standard Deviation 4.46
|
|
Albumin, Globulin, and Protein at Various Time Points Mean (Standard Deviation)
Protein (g/L) 8 days post dose (Day 9)
|
73.1 g/L
Standard Deviation 4.90
|
SECONDARY outcome
Timeframe: Day 1 pre dose, 3, 7, and 8 days post dosePopulation: All subjects which were included in the safety population which is defined as all subjects who received at least one dose of TPOXX were included in this analysis.
Table 14.3.2.2.1 Laboratory Results - Serum Chemistry Safety Population Summary tables of observed values and changes from baseline: for serum chemistry laboratory tests with numeric values for subjects in the Safety Population; to each scheduled post-baseline and changes in low, normal, high, and abnormal were summarized comparing the results at each scheduled post-baseline. Central laboratory reference ranges used for all clinical laboratory safety parameters
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Anion Gap (mmol/L) Baseline
|
10.6 mmol/L
Standard Deviation 1.5
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Anion Gap (mmol/L) 3 days post dose (Day 4)
|
10.4 mmol/L
Standard Deviation 2.15
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Anion Gap (mmol/L) 8 days post dose (Day 9)
|
10.3 mmol/L
Standard Deviation 1.38
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Blood Urea Nitrogen (mmol/L) Baseline
|
4.415 mmol/L
Standard Deviation 1.05
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Blood Urea Nitrogen (mmol/L) 3 days post dose (Day 4)
|
4.231 mmol/L
Standard Deviation 0.7147
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Blood Urea Nitrogen (mmol/L) 7 days post dose (Day 8)
|
4.091 mmol/L
Standard Deviation 0.6397
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Blood Urea Nitrogen (mmol/L) 8 days post dose (Day 9)
|
4.346 mmol/L
Standard Deviation 0.6745
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Calcium (mmol/L) Baseline
|
2.304 mmol/L
Standard Deviation 0.0980
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Calcium (mmol/L) 3 days post dose (Day 4)
|
2.360 mmol/L
Standard Deviation 0.0921
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Calcium (mmol/L) 7 days post dose (Day 8)
|
2.397 mmol/L
Standard Deviation 0.0921
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Calcium (mmol/L) 8 days post dose (Day 9)
|
2.348 mmol/L
Standard Deviation 0.0852
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Carbon Dioxide (mmol/L) 3 days post dose (Day 4)
|
29.5 mmol/L
Standard Deviation 2.02
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Carbon Dioxide (mmol/L) 7 days post dose (Day 8)
|
29.8 mmol/L
Standard Deviation 1.55
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Carbon Dioxide (mmol/L) 8 days post dose (Day 9)
|
29.4 mmol/L
Standard Deviation 1.78
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Chloride (mmol/L) Baseline
|
102.6 mmol/L
Standard Deviation 1.48
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Chloride (mmol/L) 3 days post dose (Day 4)
|
103.0 mmol/L
Standard Deviation 1.55
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Chloride (mmol/L) 7 days post dose (Day 8)
|
102.2 mmol/L
Standard Deviation 1.68
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Phosphate (mmol/L) Baseline
|
1.115 mmol/L
Standard Deviation 0.1642
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Phosphate (mmol/L) 3 days post dose (Day 4)
|
1.246 mmol/L
Standard Deviation 0.1668
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Phosphate (mmol/L) 7 days post dose (Day 8)
|
1.282 mmol/L
Standard Deviation 0.1600
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Phosphate (mmol/L) 8 days post dose (Day 9)
|
1.104 mmol/L
Standard Deviation 0.1363
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Potassium (mmol/L) Baseline
|
4.12 mmol/L
Standard Deviation 0.263
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Potassium (mmol/L) 3 days post dose (Day 4)
|
4.15 mmol/L
Standard Deviation 0.230
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Potassium (mmol/L) 7 days post dose (Day 8)
|
4.17 mmol/L
Standard Deviation 0.244
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Anion Gap (mmol/L) 7 days post dose (Day 8)
|
10.6 mmol/L
Standard Deviation 1.65
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Carbon Dioxide (mmol/L) Baseline
|
29.2 mmol/L
Standard Deviation 1.47
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Chloride (mmol/L) 8 days post dose (Day 9)
|
101.9 mmol/L
Standard Deviation 1.56
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Glucose (mmol/L) Baseline
|
5.401 mmol/L
Standard Deviation 0.4533
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Glucose (mmol/L) 3 days post dose (Day 4)
|
5.276 mmol/L
Standard Deviation 0.4118
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Glucose (mmol/L) 7 days post dose (Day 8)
|
5.088 mmol/L
Standard Deviation 0.4252
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Glucose (mmol/L) 8 days post dose (Day 9)
|
5.169 mmol/L
Standard Deviation 0.3683
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Potassium (mmol/L) 8 days post dose (Day 9)
|
4.13 mmol/L
Standard Deviation 0.303
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Sodium (mmol/L) Baseline
|
138.2 mmol/L
Standard Deviation 1.57
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Sodium (mmol/L) 3 days post dose (Day 4)
|
138.9 mmol/L
Standard Deviation 1.62
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Sodium (mmol/L) 7 days post dose (Day 8)
|
138.5 mmol/L
Standard Deviation 1.69
|
|
Average Serum Chemistry at Various Time Points; Mean (Standard Deviation)
Sodium (mmol/L) 8 days post dose (Day 9)
|
137.4 mmol/L
Standard Deviation 1.88
|
SECONDARY outcome
Timeframe: 8 days post dosePopulation: All subjects which were included in the safety population which is defined as all subjects who received at least one dose of TPOXX were included in this analysis.
Table 14.3.2.3.2 Laboratory Results - Urinalysis Safety Population Summary tables of observed values and changes from baseline: for urinalysis laboratory tests with numeric values for subjects in the Safety Population; to each scheduled post-baseline and changes in low, normal, high, and abnormal were summarized comparing the results at each scheduled post-baseline visit. Central laboratory reference ranges used for all clinical laboratory safety parameters.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Urobilinogen (Umol/dl) 8 Days Post Dose (Day 9); Mean (Standard Deviation)
|
1.0196 umol/dl
Standard Deviation 0.00640
|
SECONDARY outcome
Timeframe: 9 daysPopulation: Mean 12-lead ECG values after dosing.
Table 14.3.4.1.1 Electrocardiogram Results Safety Population Data listed shows the mean and standard deviation of 12 Lead EKG heart rate for 34 participants on day 9.
Outcome measures
| Measure |
TPOXX
n=34 Participants
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
12-lead ECG Heart Rate at 9 Day Time Point; Mean (Standard Deviation)
|
71.0 bats per minute
Standard Deviation 9.66
|
Adverse Events
TPOXX
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
TPOXX
n=34 participants at risk
TPOXX 600 mg BID x 7 days
Tpoxx: oral antiviral
|
|---|---|
|
Nervous system disorders
Headache
|
5.9%
2/34 • Number of events 2 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Nausea
|
5.9%
2/34 • Number of events 2 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Infrequent bowel movements
|
2.9%
1/34 • Number of events 1 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Gastrointestinal disorders
Lip dry
|
2.9%
1/34 • Number of events 1 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Eye disorders
Scleral hyperaemia
|
2.9%
1/34 • Number of events 1 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Infections and infestations
Urinary tract infection
|
2.9%
1/34 • Number of events 1 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Injury, poisoning and procedural complications
Palate injury
|
2.9%
1/34 • Number of events 1 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.9%
1/34 • Number of events 1 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Renal and urinary disorders
Dysuria
|
2.9%
1/34 • Number of events 1 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
2.9%
1/34 • Number of events 1 • Adverse events were collected from first dose of study drug until study Day 37 (+2 days).
An AE is any event or any untoward medical occurrence, including those AEs that result from dosing error, which may present during administration of a study drug, or during a reasonable follow-up period, and which does not necessarily have a causal relationship with this treatment.
|
Additional Information
Emily Blum, Assoc. Director of Clinical Research
SIGA Technologies
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER