Trial Outcomes & Findings for Pharmacokinetics, Safety and Tolerability of ITF2357 in Participants With Chronic Hepatic Impairment and With Normal Hepatic Function (NCT NCT06736223)
NCT ID: NCT06736223
Last Updated: 2026-06-18
Results Overview
Maximum plasma concentration observed
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose
Results posted on
2026-06-18
Participant Flow
A total of 24 participants, 8 participants in each group, were enrolled and completed the study.
Thirty-one (31) participants were screened; 7 failed screening. In the NHF group, 4 did not meet criteria, 1 was eligible but not needed, and 1 withdrew consent. In the Mild HI group, 1 was eligible but not needed. All Moderate HI participants were included.
Participant milestones
| Measure |
Mild HI
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
Patients with moderate HI (Child-Pugh class B)
|
Healthy Volunteers
Participants with normal hepatic function (control group)
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Child-Pugh score was not assessed for participants with normal hepatic function.
Baseline characteristics by cohort
| Measure |
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.1 year
STANDARD_DEVIATION 8.44 • n=8 Participants
|
61.9 year
STANDARD_DEVIATION 7.51 • n=8 Participants
|
38.6 year
STANDARD_DEVIATION 13.09 • n=8 Participants
|
51.5 year
STANDARD_DEVIATION 13.73 • n=24 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
10 Participants
n=24 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
14 Participants
n=24 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
3 Participants
n=24 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
21 Participants
n=24 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
24 Participants
n=24 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Weight
Weight at screening
|
77.89 kg
STANDARD_DEVIATION 22.701 • n=8 Participants
|
78.98 kg
STANDARD_DEVIATION 21.303 • n=8 Participants
|
79.04 kg
STANDARD_DEVIATION 2.274 • n=8 Participants
|
78.63 kg
STANDARD_DEVIATION 17.228 • n=24 Participants
|
|
Weight
Weight at D-1
|
77.71 kg
STANDARD_DEVIATION 22.502 • n=8 Participants
|
79.04 kg
STANDARD_DEVIATION 21.140 • n=8 Participants
|
79.54 kg
STANDARD_DEVIATION 1.907 • n=8 Participants
|
78.76 kg
STANDARD_DEVIATION 17.074 • n=24 Participants
|
|
BMI
BMI at screening
|
26.605 kg/m2
STANDARD_DEVIATION 6.2639 • n=8 Participants
|
27.248 kg/m2
STANDARD_DEVIATION 6.2722 • n=8 Participants
|
26.653 kg/m2
STANDARD_DEVIATION 2.1064 • n=8 Participants
|
26.835 kg/m2
STANDARD_DEVIATION 5.0353 • n=24 Participants
|
|
BMI
BMI at D-1
|
26.553 kg/m2
STANDARD_DEVIATION 6.2306 • n=8 Participants
|
27.273 kg/m2
STANDARD_DEVIATION 6.2001 • n=8 Participants
|
26.823 kg/m2
STANDARD_DEVIATION 2.1284 • n=8 Participants
|
26.883 kg/m2
STANDARD_DEVIATION 4.9985 • n=24 Participants
|
|
Child-Pugh score
Child-Pugh score at screening
|
5.00 Scores on a scale (5 to 15)
STANDARD_DEVIATION 0.000 • n=8 Participants • Child-Pugh score was not assessed for participants with normal hepatic function.
|
7.13 Scores on a scale (5 to 15)
STANDARD_DEVIATION 0.354 • n=8 Participants • Child-Pugh score was not assessed for participants with normal hepatic function.
|
—
|
6.06 Scores on a scale (5 to 15)
STANDARD_DEVIATION 1.124 • n=16 Participants • Child-Pugh score was not assessed for participants with normal hepatic function.
|
|
Child-Pugh score
Child-Pugh score at D-1
|
5.00 Scores on a scale (5 to 15)
STANDARD_DEVIATION 0.000 • n=8 Participants • Child-Pugh score was not assessed for participants with normal hepatic function.
|
7.38 Scores on a scale (5 to 15)
STANDARD_DEVIATION 0.518 • n=8 Participants • Child-Pugh score was not assessed for participants with normal hepatic function.
|
—
|
6.19 Scores on a scale (5 to 15)
STANDARD_DEVIATION 1.276 • n=16 Participants • Child-Pugh score was not assessed for participants with normal hepatic function.
|
PRIMARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseMaximum plasma concentration observed
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Cmax of ITF2357
|
47.21 ng/mL
Geometric Coefficient of Variation 34.6
|
42.54 ng/mL
Geometric Coefficient of Variation 33.5
|
39.19 ng/mL
Geometric Coefficient of Variation 54.7
|
PRIMARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseArea under the plasma concentration versus time curve to the real time tlast
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
AUClast of ITF2357
|
306.20 h*ng/mL
Geometric Coefficient of Variation 25.0
|
272.17 h*ng/mL
Geometric Coefficient of Variation 38.1
|
207.85 h*ng/mL
Geometric Coefficient of Variation 43.3
|
PRIMARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseArea under the plasma concentration versus time curve extrapolated to infinity
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
AUC0-inf of ITF2357
|
319.45 h*ng/mL
Geometric Coefficient of Variation 23.7
|
287.92 h*ng/mL
Geometric Coefficient of Variation 36.7
|
223.54 h*ng/mL
Geometric Coefficient of Variation 41.9
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseTime to reach Cmax
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Tmax of ITF2357
|
1.000 hours
Full Range 1.000-5.00 • Interval 1.0 to 5.0
|
2.000 hours
Full Range 1.00-4.00 • Interval 1.0 to 4.0
|
2.000 hours
Full Range 0.50-4.00 • Interval 0.5 to 4.0
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseApparent terminal half-life
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
t1/2 of ITF2357
|
7.0450 hours
Geometric Coefficient of Variation 10.6
|
7.8876 hours
Geometric Coefficient of Variation 14.5
|
7.7619 hours
Geometric Coefficient of Variation 22.4
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseApparent total plasma clearance from plasma
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
CL/F of ITF2357
|
156.5170 L/h
Geometric Coefficient of Variation 23.7
|
173.6618 L/h
Geometric Coefficient of Variation 36.7
|
223.6763 L/h
Geometric Coefficient of Variation 41.9
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseApparent volume of distribution
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Vz/F of ITF2357
|
1590.7968 L
Geometric Coefficient of Variation 24.0
|
1976.1675 L
Geometric Coefficient of Variation 31.8
|
2504.7280 L
Geometric Coefficient of Variation 39.3
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseMaximum plasma concentration observed
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Cmax of ITF2357 Metabolites
ITF2374
|
7.57 ng/mL
Geometric Coefficient of Variation 36.9
|
6.34 ng/mL
Geometric Coefficient of Variation 41.4
|
6.11 ng/mL
Geometric Coefficient of Variation 36.5
|
|
Cmax of ITF2357 Metabolites
ITF2375
|
125.30 ng/mL
Geometric Coefficient of Variation 28.4
|
108.28 ng/mL
Geometric Coefficient of Variation 55.3
|
82.31 ng/mL
Geometric Coefficient of Variation 45.6
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseArea under the plasma concentration versus time curve to the real time tlast
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
AUClast of ITF2357 Metabolites
ITF2374
|
179.47 h*ng/mL
Geometric Coefficient of Variation 75.6
|
138.59 h*ng/mL
Geometric Coefficient of Variation 55.3
|
118.87 h*ng/mL
Geometric Coefficient of Variation 37.4
|
|
AUClast of ITF2357 Metabolites
ITF2375
|
1588.77 h*ng/mL
Geometric Coefficient of Variation 91.3
|
1160.24 h*ng/mL
Geometric Coefficient of Variation 74.6
|
835.66 h*ng/mL
Geometric Coefficient of Variation 47.0
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dosePopulation: No descriptive data computed when more than half of the values were not analyzable or missing.
Area under the plasma concentration versus time curve extrapolated to infinity
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
AUC0-inf of ITF2357 Metabolites
ITF2374
|
239.11 h*ng/mL
Geometric Coefficient of Variation 59.8
|
NA h*ng/mL
Geometric Coefficient of Variation NA
No descriptive data computed when more than half of the values were not analyzable or missing.
|
165.95 h*ng/mL
Geometric Coefficient of Variation 27.2
|
|
AUC0-inf of ITF2357 Metabolites
ITF2375
|
1630.94 h*ng/mL
Geometric Coefficient of Variation 89.2
|
1195.40 h*ng/mL
Geometric Coefficient of Variation 74.5
|
865.47 h*ng/mL
Geometric Coefficient of Variation 46.0
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseTime to reach Cmax
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Tmax of ITF2357 Metabolites
ITF2374
|
12.000 hours
Interval 3.0 to 24.0
|
6.000 hours
Interval 4.0 to 10.0
|
5.000 hours
Interval 4.0 to 10.02
|
|
Tmax of ITF2357 Metabolites
ITF2375
|
2.500 hours
Interval 2.03 to 10.0
|
2.500 hours
Interval 2.5 to 4.0
|
3.000 hours
Interval 2.0 to 3.0
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dosePopulation: Descriptive statistics were not computed when more than half of the values were not analyzable or missing (ITF2374: Mild HI n=2)
Apparent terminal half-life
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
t1/2 of ITF2357 Metabolites
ITF2374
|
14.1083 hours
Geometric Coefficient of Variation 47.4
|
NA hours
Geometric Coefficient of Variation NA
No descriptive data computed when more than half of the values were not analyzable or missing
|
12.3264 hours
Geometric Coefficient of Variation 12.0
|
|
t1/2 of ITF2357 Metabolites
ITF2375
|
13.9453 hours
Geometric Coefficient of Variation 25.6
|
13.6579 hours
Geometric Coefficient of Variation 35.8
|
12.5157 hours
Geometric Coefficient of Variation 24.3
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseUnbound fraction (fu) is the fraction of total plasma drug concentration that is not bound to plasma proteins and is pharmacologically available
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Fu of ITF2357 and Its Metabolites
ITF2357
|
3.7642 % of unbound fraction
Geometric Coefficient of Variation 17.1
|
4.5044 % of unbound fraction
Geometric Coefficient of Variation 22.7
|
4.8945 % of unbound fraction
Geometric Coefficient of Variation 21.8
|
|
Fu of ITF2357 and Its Metabolites
ITF2374
|
7.4527 % of unbound fraction
Geometric Coefficient of Variation 18.7
|
8.0631 % of unbound fraction
Geometric Coefficient of Variation 14.0
|
8.5972 % of unbound fraction
Geometric Coefficient of Variation 13.6
|
|
Fu of ITF2357 and Its Metabolites
ITF2375
|
1.0433 % of unbound fraction
Geometric Coefficient of Variation 11.6
|
1.1150 % of unbound fraction
Geometric Coefficient of Variation 11.9
|
1.2801 % of unbound fraction
Geometric Coefficient of Variation 19.2
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseUnbound area under the plasma concentration versus time curve to the real time Tlast
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
AUC0-last,u of ITF2357 and Its Metabolites
ITF2357
|
11.53 h*ng/mL
Geometric Coefficient of Variation 36.2
|
12.26 h*ng/mL
Geometric Coefficient of Variation 41.5
|
10.17 h*ng/mL
Geometric Coefficient of Variation 35.5
|
|
AUC0-last,u of ITF2357 and Its Metabolites
ITF2374
|
13.38 h*ng/mL
Geometric Coefficient of Variation 86.1
|
11.18 h*ng/mL
Geometric Coefficient of Variation 54.2
|
10.47 h*ng/mL
Geometric Coefficient of Variation 37.9
|
|
AUC0-last,u of ITF2357 and Its Metabolites
ITF2375
|
16.58 h*ng/mL
Geometric Coefficient of Variation 86.5
|
12.94 h*ng/mL
Geometric Coefficient of Variation 65.5
|
10.70 h*ng/mL
Geometric Coefficient of Variation 46.3
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dosePopulation: Descriptive statistics were not computed when more than half of the value were not analyzable or missing
Unbound area under the plasma concentration versus time extrapolated to infinity
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
AUC0-inf,u of ITF2357 and Its Metabolites
ITF2357
|
12.02 h*ng/mL
Geometric Coefficient of Variation 34.8
|
12.97 h*ng/mL
Geometric Coefficient of Variation 40.1
|
10.94 h*ng/mL
Geometric Coefficient of Variation 34.7
|
|
AUC0-inf,u of ITF2357 and Its Metabolites
ITF2374
|
17.73 h*ng/mL
Geometric Coefficient of Variation 58.8
|
NA h*ng/mL
Geometric Coefficient of Variation NA
No descriptive data computed when more than half of the values were not analyzable or missing (ITF2374: Mild HI n=2)
|
12.72 h*ng/mL
Geometric Coefficient of Variation 31.8
|
|
AUC0-inf,u of ITF2357 and Its Metabolites
ITF2375
|
17.02 h*ng/mL
Geometric Coefficient of Variation 84.6
|
13.33 h*ng/mL
Geometric Coefficient of Variation 65.4
|
11.08 h*ng/mL
Geometric Coefficient of Variation 45.4
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseUnbound maximum plasma concentration observed
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Cmax,u of ITF2357 and Its Metabolites
ITF2357
|
1.78 ng/mL
Geometric Coefficient of Variation 37.6
|
1.92 ng/mL
Geometric Coefficient of Variation 44.4
|
1.92 ng/mL
Geometric Coefficient of Variation 46.5
|
|
Cmax,u of ITF2357 and Its Metabolites
ITF2374
|
0.56 ng/mL
Geometric Coefficient of Variation 41.6
|
0.51 ng/mL
Geometric Coefficient of Variation 46.6
|
0.52 ng/mL
Geometric Coefficient of Variation 30.8
|
|
Cmax,u of ITF2357 and Its Metabolites
ITF2375
|
1.31 ng/mL
Geometric Coefficient of Variation 27.9
|
1.21 ng/mL
Geometric Coefficient of Variation 53.2
|
1.05 ng/mL
Geometric Coefficient of Variation 45.9
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseUnbound apparent total plasma clearance
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
CL/Fu of ITF2357
|
4158.0773 L/h
Geometric Coefficient of Variation 34.8
|
3855.3955 L/h
Geometric Coefficient of Variation 40.1
|
4569.9699 L/h
Geometric Coefficient of Variation 34.7
|
SECONDARY outcome
Timeframe: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-doseUnbound apparent volume of distribution
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Vz/Fu of ITF2357
|
42261.5883 L
Geometric Coefficient of Variation 35.8
|
43872.1021 L
Geometric Coefficient of Variation 37.8
|
51174.5320 L
Geometric Coefficient of Variation 34.1
|
SECONDARY outcome
Timeframe: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one related TEAEs. Treatment Emergent Adverse Event is defined as any untoward medical occurrence (including an abnormal laboratory finding, symptom or a disease) in a participant administered the pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment.
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Incidence of Treatment Emergent Adverse Events (TEAEs)
|
1 Participants
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one related TEAEs
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Incidence of Treatment-Related TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one TEAEs according to NCI-CTCAE grade version 5.0, where severity is classified as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe or medically significant), Grade 4 (life-threatening), and Grade 5 (death related to the adverse event).
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Severity of Treatment Emergent Adverse Events (TEAEs)
Grade 1
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Severity of Treatment Emergent Adverse Events (TEAEs)
Grade 2
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Severity of Treatment Emergent Adverse Events (TEAEs)
Grade ≥ 3
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one TEAE leading to withdrawal from the study
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Incidence of TEAEs Leading to Withdrawal From the Study
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From screening (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one Serious TEAE
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Incidence of Serious TEAEs (SAEs)
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one clinically significant laboratory parameters abnormality. The following parameters were measured: Hematology: Hemoglobin, hematocrit, erythrocytes, platelets, leukocytes, and differential counts (basophils, eosinophils, lymphocytes, monocytes, neutrophils). Blood chemistry: Sodium, potassium, chloride, calcium, urea, creatinine, albumin, glucose, total proteins, triglycerides, total cholesterol, ALT, AST, GGT, CPK, alkaline phosphatase, total bilirubin. Coagulation: PT, INR, aPTT. Serology: HBsAg, anti-HBc, anti-HCV, anti-HIV-1/2, pregnancy test (hCG). Urinalysis: pH, protein, glucose, leukocytes, nitrites, ketones, blood. Other: Alcohol breath test; urine drug screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Incidence of Clinically Significant Clinical Laboratory Parameters Abnormality
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one clinically significant vitals abnormality. The following clinical signs were measured: body temperature (C°), supine systolic blood pressure (mmHg), diastolic blood pressure (mmHg), pulse rate (beats/min), and respiratory rate (breath/min).
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Incidence of Clinically Significant Vital Signs Abnormality
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one clinically significant electrocardiogram abnormality. The following standard 12-lead ECG were recorded: heart rate (beats/min), PR interval (msec), QRS duration (msec), QRS axis (deg), QT interval (msec) and Fridericia and Bazett QTc interval (msec)
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Incidence of Clinically Significant Electrocardiogram Abnormality
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration)Number of participants with at least one clinically significant physical abnormality. A complete physical examination, including at a minimum assessments of the cardiovascular, respiratory, gastrointestinal, dermatological, neurological, and musculoskeletal systems, in addition to examinations of the head, eyes, ears, nose, throat, neck, and lymph nodes, as well as height and weight measurement.
Outcome measures
| Measure |
Healthy Volunteers
n=8 Participants
Participants with normal hepatic function (control group)
|
Mild HI
n=8 Participants
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 Participants
Patients with moderate HI (Child-Pugh class B)
|
|---|---|---|---|
|
Incidence of Clinically Significant Physical Examination Abnormality
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Mild HI
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Moderate HI
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Healthy Volunteers
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Mild HI
n=8 participants at risk
Patients with mild HI (Child-Pugh class A)
|
Moderate HI
n=8 participants at risk
Patients with moderate HI (Child-Pugh class B)
|
Healthy Volunteers
n=8 participants at risk
Participants with normal hepatic function (control group)
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
12.5%
1/8 • Number of events 1 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
0.00%
0/8 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/8 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
12.5%
1/8 • Number of events 1 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
0.00%
0/8 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/8 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
0.00%
0/8 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
12.5%
1/8 • Number of events 1 • AEs were recorded from the time of informed consent through the EOS visit.
AE was coded described by the seriousness, duration (start and end dates), NCI-CTCAE version 5.0 Grade, relationship with drug study, outcome.
|
Additional Information
Maurizio Caserini, Responsible medical officer
Italfarmaco SpA
Phone: +39 02 6443 1
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place