Trial Outcomes & Findings for PK and PD Study of IDN-6556 in Subjects With Hepatic Impairment and Matched Healthy Volunteers (NCT NCT02121860)
NCT ID: NCT02121860
Last Updated: 2016-02-24
Results Overview
Area under the plasma concentration curve (AUC) to 12 hours post-dose (AUC0-12); AUC to the last observed plasma concentration (AUClast);
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
37 participants
Primary outcome timeframe
48 Hours
Results posted on
2016-02-24
Participant Flow
This was an open-label, multicenter, parallel-group study to compare the PK and PD of IDN 6556 following a single 50 mg oral dose of IDN-6556 in subjects with mild, moderate, and severe hepatic impairment (defined as Child-Pugh A, B, and C, respectively) and matched healthy volunteers (subjects with normal hepatic function).
A total of 37 subjects were dosed. One subject was dosed twice at two different centers, so the analyzed sample size was 36 subjects: 12 subjects with mild, and 8 subjects each with moderate and severe hepatic impairment, and with normal hepatic function.
Participant milestones
| Measure |
Normal Hepatic Function
Medically healthy as determined by the investigator
|
Child-Pugh Class A
Mild hepatic impairment
|
Child-Pugh Class B
Moderate hepatic impairment
|
Child-Pugh Class C
Severe hepatic impairment
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
12
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
12
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PK and PD Study of IDN-6556 in Subjects With Hepatic Impairment and Matched Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Child-Pugh Class A
n=12 Participants
Mild Hepatic Impairment
|
Child-Pugh Class B
n=8 Participants
Moderate Hepatic Impairment
|
Child-Pugh Class C
n=8 Participants
Severe Hepatic Impairment
|
Normal Hepatic Function
n=8 Participants
Medically healthy as determined by the investigator
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
54.8 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
54.1 years
STANDARD_DEVIATION 7.1 • n=7 Participants
|
57.4 years
STANDARD_DEVIATION 4.8 • n=5 Participants
|
57.6 years
STANDARD_DEVIATION 4.9 • n=4 Participants
|
55.9 years
STANDARD_DEVIATION 6.8 • n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
33 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
8 participants
n=7 Participants
|
8 participants
n=5 Participants
|
8 participants
n=4 Participants
|
36 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 48 HoursPopulation: The analyzed sample size was 36 subjects: 12 subjects with mild, and 8 subjects each with moderate and severe hepatic impairment, and with normal hepatic function.
Area under the plasma concentration curve (AUC) to 12 hours post-dose (AUC0-12); AUC to the last observed plasma concentration (AUClast);
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Medically healthy as determined by the investigator
|
Child-Pugh Class A
n=12 Participants
Mild Hepatic Impairment
|
Child-Pugh Class B
n=8 Participants
Moderate Hepatic Impairment
|
Child-Pugh Class C
n=8 Participants
Severe Hepatic Impairment
|
|---|---|---|---|---|
|
AUC
AUC0-12 (h*ng/mL)
|
113.5 h*ng/mL
Geometric Coefficient of Variation 51.1
|
114.6 h*ng/mL
Geometric Coefficient of Variation 36.0
|
423.7 h*ng/mL
Geometric Coefficient of Variation 126.1
|
1042 h*ng/mL
Geometric Coefficient of Variation 27.8
|
|
AUC
AUClast (h*ng/mL)
|
120.6 h*ng/mL
Geometric Coefficient of Variation 47.1
|
118.2 h*ng/mL
Geometric Coefficient of Variation 33.0
|
435.7 h*ng/mL
Geometric Coefficient of Variation 121.7
|
1083 h*ng/mL
Geometric Coefficient of Variation 26.9
|
PRIMARY outcome
Timeframe: 48 HoursMaximum concentration (Cmax)
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Medically healthy as determined by the investigator
|
Child-Pugh Class A
n=12 Participants
Mild Hepatic Impairment
|
Child-Pugh Class B
n=8 Participants
Moderate Hepatic Impairment
|
Child-Pugh Class C
n=8 Participants
Severe Hepatic Impairment
|
|---|---|---|---|---|
|
Cmax
|
26.01 ng/mL
Geometric Coefficient of Variation 70.4
|
37.45 ng/mL
Geometric Coefficient of Variation 64.9
|
127.2 ng/mL
Geometric Coefficient of Variation 146.6
|
322.2 ng/mL
Geometric Coefficient of Variation 40.9
|
SECONDARY outcome
Timeframe: predose, 0.5, 1,2,3,4,5,8,12,24, and 48 hours post doseCaspase-cleaved cytokeratin levels (cCK18M30)
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Medically healthy as determined by the investigator
|
Child-Pugh Class A
n=12 Participants
Mild Hepatic Impairment
|
Child-Pugh Class B
n=8 Participants
Moderate Hepatic Impairment
|
Child-Pugh Class C
n=8 Participants
Severe Hepatic Impairment
|
|---|---|---|---|---|
|
Levels of cCK18/M30
Predose
|
161.5 U/L
Interval 123.0 to 236.0
|
147.5 U/L
Interval 110.5 to 293.5
|
348.0 U/L
Interval 200.0 to 601.5
|
517.0 U/L
Interval 340.5 to 552.5
|
|
Levels of cCK18/M30
0.5 hour post dose
|
147.0 U/L
Interval 141.5 to 174.0
|
153.0 U/L
Interval 124.0 to 322.5
|
433.5 U/L
Interval 188.0 to 578.5
|
506.5 U/L
Interval 348.5 to 551.5
|
|
Levels of cCK18/M30
1 hour post dose
|
155.5 U/L
Interval 139.0 to 189.0
|
170.5 U/L
Interval 122.0 to 276.5
|
380.5 U/L
Interval 224.5 to 560.0
|
471.0 U/L
Interval 344.0 to 499.5
|
|
Levels of cCK18/M30
2 hours post dose
|
149.0 U/L
Interval 130.5 to 183.0
|
153.0 U/L
Interval 109.0 to 247.0
|
376.5 U/L
Interval 205.0 to 471.0
|
446.5 U/L
Interval 345.0 to 531.0
|
|
Levels of cCK18/M30
3 hours post dose
|
181.5 U/L
Interval 146.5 to 212.5
|
167.0 U/L
Interval 108.5 to 250.5
|
322.5 U/L
Interval 176.0 to 422.0
|
388.0 U/L
Interval 307.0 to 493.5
|
|
Levels of cCK18/M30
4 hours post dose
|
161.5 U/L
Interval 144.0 to 190.0
|
156.5 U/L
Interval 110.5 to 249.0
|
295.5 U/L
Interval 196.0 to 361.0
|
362.0 U/L
Interval 287.0 to 437.5
|
|
Levels of cCK18/M30
5 hours post dose
|
157.5 U/L
Interval 138.5 to 184.5
|
161.5 U/L
Interval 102.0 to 187.0
|
229.0 U/L
Interval 164.5 to 350.0
|
358.0 U/L
Interval 243.5 to 415.0
|
|
Levels of cCK18/M30
8 hours post dose
|
146.0 U/L
Interval 127.5 to 205.0
|
126.0 U/L
Interval 104.0 to 172.0
|
190.5 U/L
Interval 110.5 to 307.0
|
274.5 U/L
Interval 208.5 to 343.0
|
|
Levels of cCK18/M30
12 hours post dose
|
175.5 U/L
Interval 135.0 to 219.5
|
104.5 U/L
Interval 84.5 to 164.5
|
137.5 U/L
Interval 110.5 to 249.5
|
287.5 U/L
Interval 164.0 to 356.0
|
|
Levels of cCK18/M30
24 hours post dose
|
163.5 U/L
Interval 134.0 to 191.5
|
151.0 U/L
Interval 104.0 to 213.5
|
298.0 U/L
Interval 183.0 to 339.5
|
423.0 U/L
Interval 331.5 to 488.0
|
|
Levels of cCK18/M30
48 hours post dose
|
213.0 U/L
Interval 141.0 to 269.5
|
193.0 U/L
Interval 121.5 to 283.0
|
353.5 U/L
Interval 244.0 to 555.5
|
508.5 U/L
Interval 381.0 to 581.5
|
SECONDARY outcome
Timeframe: predose, 0.5, 1,2,3,4,5,8,12,24, and 48 hours post doseConcentration of Caspase 3/7 Relative Light Units
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Medically healthy as determined by the investigator
|
Child-Pugh Class A
n=12 Participants
Mild Hepatic Impairment
|
Child-Pugh Class B
n=8 Participants
Moderate Hepatic Impairment
|
Child-Pugh Class C
n=8 Participants
Severe Hepatic Impairment
|
|---|---|---|---|---|
|
Levels of Caspase 3/7 RLU
8 hours post dose
|
916.0 RLU
Interval 797.5 to 1263.0
|
1088.5 RLU
Interval 929.0 to 1216.5
|
1084.5 RLU
Interval 921.5 to 1410.0
|
893.5 RLU
Interval 750.5 to 1275.5
|
|
Levels of Caspase 3/7 RLU
Predose
|
963.5 RLU
Interval 753.5 to 1554.0
|
1158.5 RLU
Interval 862.5 to 1547.5
|
2006.0 RLU
Interval 1537.0 to 2394.5
|
1662.5 RLU
Interval 1256.5 to 2194.0
|
|
Levels of Caspase 3/7 RLU
.5 hour post dose
|
900.5 RLU
Interval 835.5 to 1398.5
|
1130.5 RLU
Interval 852.5 to 1386.0
|
2027.0 RLU
Interval 1391.5 to 2276.0
|
1933.5 RLU
Interval 1557.0 to 2915.0
|
|
Levels of Caspase 3/7 RLU
1 hour post dose
|
850.5 RLU
Interval 766.5 to 1078.5
|
1260.5 RLU
Interval 814.5 to 1297.5
|
1482.0 RLU
Interval 1169.0 to 1821.0
|
1392.0 RLU
Interval 1096.0 to 1814.5
|
|
Levels of Caspase 3/7 RLU
2 hours post dose
|
820.0 RLU
Interval 772.0 to 1111.0
|
1048.0 RLU
Interval 873.5 to 1311.5
|
1121.0 RLU
Interval 961.5 to 1270.0
|
1090.0 RLU
Interval 674.5 to 1482.0
|
|
Levels of Caspase 3/7 RLU
3 hours post dose
|
872.0 RLU
Interval 746.5 to 1084.5
|
1027.0 RLU
Interval 888.5 to 1170.5
|
906.5 RLU
Interval 858.0 to 1238.5
|
796.0 RLU
Interval 618.0 to 958.5
|
|
Levels of Caspase 3/7 RLU
4 hours post dose
|
848.5 RLU
Interval 789.0 to 1085.0
|
921.0 RLU
Interval 795.5 to 1097.0
|
984.5 RLU
Interval 887.0 to 1170.0
|
806.5 RLU
Interval 571.0 to 949.5
|
|
Levels of Caspase 3/7 RLU
5 hours post dose
|
836.5 RLU
Interval 792.5 to 1142.0
|
976.0 RLU
Interval 823.0 to 1178.0
|
903.5 RLU
Interval 856.5 to 1312.5
|
776.0 RLU
Interval 694.5 to 935.5
|
|
Levels of Caspase 3/7 RLU
12 hours post dose
|
876.5 RLU
Interval 686.5 to 1002.0
|
1039.0 RLU
Interval 793.0 to 1170.5
|
1230.5 RLU
Interval 992.0 to 1516.5
|
1187.0 RLU
Interval 924.5 to 1478.0
|
|
Levels of Caspase 3/7 RLU
24 hours post dose
|
842.0 RLU
Interval 723.5 to 1060.0
|
1227.5 RLU
Interval 949.5 to 1344.5
|
1798.5 RLU
Interval 1308.5 to 2128.5
|
1276.0 RLU
Interval 1027.0 to 2907.5
|
|
Levels of Caspase 3/7 RLU
48 hours post dose
|
991.5 RLU
Interval 719.5 to 1149.5
|
1291.0 RLU
Interval 877.5 to 1534.0
|
1754.0 RLU
Interval 1440.5 to 2243.5
|
1457.5 RLU
Interval 1097.0 to 2685.0
|
Adverse Events
IDN-6556
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
IDN-6556
n=36 participants at risk
Single 50 mg oral dose of IDN-6556
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
5.6%
2/36 • Number of events 2 • 10 Days
|
|
Cardiac disorders
tachycardia
|
2.8%
1/36 • Number of events 1 • 10 Days
|
|
Infections and infestations
Gastroenteritis
|
2.8%
1/36 • Number of events 1 • 10 Days
|
|
Gastrointestinal disorders
Dyspepsia
|
2.8%
1/36 • Number of events 1 • 10 Days
|
|
Gastrointestinal disorders
Nausea
|
2.8%
1/36 • Number of events 1 • 10 Days
|
|
Gastrointestinal disorders
Vomiting
|
2.8%
1/36 • Number of events 1 • 10 Days
|
|
Infections and infestations
Pulpitis Dental
|
2.8%
1/36 • Number of events 1 • 10 Days
|
|
Nervous system disorders
headache
|
8.3%
3/36 • Number of events 3 • 10 Days
|
|
Investigations
Lipase increased
|
2.8%
1/36 • Number of events 2 • 10 Days
|
|
Investigations
Transaminases increased
|
2.8%
1/36 • Number of events 1 • 10 Days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60