Trial Outcomes & Findings for A Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function (NCT NCT04226833)
NCT ID: NCT04226833
Last Updated: 2024-08-02
Results Overview
Maximum observed plasma concentration. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
38 participants
Primary outcome timeframe
From Day 1 to Day 7
Results posted on
2024-08-02
Participant Flow
Participants with reduced hepatic function were assigned to a functional category based on assessments at the Screening visit.
Participant milestones
| Measure |
Mild
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Moderate
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Normal
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
12
|
11
|
8
|
|
Overall Study
COMPLETED
|
7
|
12
|
10
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Mild
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Moderate
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Normal
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Overall Study
Death
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function
Baseline characteristics by cohort
| Measure |
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
59.9 Years
STANDARD_DEVIATION 8.86 • n=93 Participants
|
58.0 Years
STANDARD_DEVIATION 9.49 • n=4 Participants
|
57.3 Years
STANDARD_DEVIATION 10.08 • n=27 Participants
|
54.3 Years
STANDARD_DEVIATION 11.99 • n=483 Participants
|
57.3 Years
STANDARD_DEVIATION 9.88 • n=36 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
9 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
29 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
38 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Maximum observed plasma concentration. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units
Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Entrectinib
|
235.990 nmol/L
Geometric Coefficient of Variation 46.1
|
213.570 nmol/L
Geometric Coefficient of Variation 36.7
|
183.680 nmol/L
Geometric Coefficient of Variation 34.3
|
296.140 nmol/L
Geometric Coefficient of Variation 40.6
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Entrectinib
|
3512.7 h*nmol/L
Geometric Coefficient of Variation 50.8
|
5401.9 h*nmol/L
Geometric Coefficient of Variation 49.1
|
6329.0 h*nmol/L
Geometric Coefficient of Variation 58.5
|
5525.6 h*nmol/L
Geometric Coefficient of Variation 47.0
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUClast) of Entrectinib
|
3283.2 h*nmol/L
Geometric Coefficient of Variation 51.5
|
4952.3 h*nmol/L
Geometric Coefficient of Variation 49.0
|
5747.9 h*nmol/L
Geometric Coefficient of Variation 53.6
|
5263.9 h*nmol/L
Geometric Coefficient of Variation 48.4
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7First observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units
Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Time of Maximum Observed Plasma Concentration (Tmax) of Entrectinib
|
2.950 h
Interval 1.0 to 4.88
|
5.000 h
Interval 2.95 to 8.05
|
3.000 h
Interval 1.0 to 5.97
|
4.000 h
Interval 2.05 to 4.83
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Half-life (t1/2) of Entrectinib
|
21.34 h
Geometric Coefficient of Variation 36.8
|
30.43 h
Geometric Coefficient of Variation 36.5
|
43.92 h
Geometric Coefficient of Variation 30.2
|
30.75 h
Geometric Coefficient of Variation 18.7
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (Lz) of Entrectinib
|
0.0345 1/h
Standard Deviation 0.01359
|
0.0241 1/h
Standard Deviation 0.00858
|
0.0165 1/h
Standard Deviation 0.00544
|
0.0229 1/h
Standard Deviation 0.00430
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Obtained by dividing the total dose of parent drug by its corresponding AUCinf
Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Apparent Oral Clearance (CL/F) of Entrectinib
|
0.0300 mg/(h*nmol/L)
Geometric Coefficient of Variation 50.8
|
0.0200 mg/(h*nmol/L)
Geometric Coefficient of Variation 49.1
|
43.92 mg/(h*nmol/L)
Geometric Coefficient of Variation 30.2
|
0.0200 mg/(h*nmol/L)
Geometric Coefficient of Variation 47.0
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Obtained by dividing Dose by the product of AUCinf and λz
Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
The Apparent Volume of Distribution (Vz/F) of Entrectinib
|
0.8800 mg/(nmol/L)
Geometric Coefficient of Variation 43.8
|
0.8100 mg/(nmol/L)
Geometric Coefficient of Variation 37.6
|
1.0000 mg/(nmol/L)
Geometric Coefficient of Variation 35.2
|
0.8000 mg/(nmol/L)
Geometric Coefficient of Variation 47.7
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Maximum observed plasma concentration. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units
Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of M5
|
60.330 nmol/L
Geometric Coefficient of Variation 41.7
|
26.390 nmol/L
Geometric Coefficient of Variation 68.6
|
17.710 nmol/L
Geometric Coefficient of Variation 58.3
|
41.310 nmol/L
Geometric Coefficient of Variation 71.0
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of M5
|
2229.9 h*nmol/L
Geometric Coefficient of Variation 40.3
|
2024.3 h*nmol/L
Geometric Coefficient of Variation 58.8
|
NA h*nmol/L
Geometric Coefficient of Variation NA
Below the level of detection
|
2432.1 h*nmol/L
Geometric Coefficient of Variation 17.2
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUClast) of M5
|
1715.6 h*nmol/L
Geometric Coefficient of Variation 48.7
|
1297.3 h*nmol/L
Geometric Coefficient of Variation 52.4
|
1202.8 h*nmol/L
Geometric Coefficient of Variation 62.9
|
1255.2 h*nmol/L
Geometric Coefficient of Variation 67.8
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7First observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units
Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Time of Maximum Observed Plasma Concentration (Tmax) of M5
|
4.985 h
Interval 2.98 to 7.97
|
5.955 h
Interval 3.0 to 35.5
|
4.920 h
Interval 2.83 to 71.8
|
5.000 h
Interval 4.83 to 8.0
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (Lz) of M5
|
0.0200 1/h
Standard Deviation 22.8
|
0.0200 1/h
Standard Deviation 30.4
|
NA 1/h
Standard Deviation NA
Below the level of detection
|
0.02000 1/h
Standard Deviation 2.5
|
PRIMARY outcome
Timeframe: From Day 1 to Day 7Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Half-life (t1/2) of M5
|
38.33 h
Geometric Coefficient of Variation 22.8
|
39.50 h
Geometric Coefficient of Variation 30.4
|
NA h
Geometric Coefficient of Variation NA
Below the level of detection
|
43.60 h
Geometric Coefficient of Variation 2.5
|
SECONDARY outcome
Timeframe: 4 weeksAE=adverse event TEAE=treatment-emergent adverse event
Outcome measures
| Measure |
Normal
n=8 Participants
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Moderate
n=12 Participants
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Severe
n=11 Participants
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
Mild
n=7 Participants
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Total Subjects With at Least 1 AE
|
2 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Subjects With at Least 1 TEAE
|
2 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Total Subjects with at Least 1 Serious TEAE
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
Adverse Events
Entrectinib - Normal
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Entrectinib Mild
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Entrectinib Moderate
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Entrectinib Severe
Serious events: 1 serious events
Other events: 2 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Entrectinib - Normal
n=8 participants at risk
Participants received 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Entrectinib Mild
n=7 participants at risk
Participants received 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Entrectinib Moderate
n=12 participants at risk
Participants received 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Entrectinib Severe
n=11 participants at risk
Participants received 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/8 • Baseline up to 4 Weeks
|
0.00%
0/7 • Baseline up to 4 Weeks
|
0.00%
0/12 • Baseline up to 4 Weeks
|
9.1%
1/11 • Number of events 1 • Baseline up to 4 Weeks
|
Other adverse events
| Measure |
Entrectinib - Normal
n=8 participants at risk
Participants received 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Entrectinib Mild
n=7 participants at risk
Participants received 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Entrectinib Moderate
n=12 participants at risk
Participants received 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
Entrectinib Severe
n=11 participants at risk
Participants received 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
25.0%
2/8 • Number of events 2 • Baseline up to 4 Weeks
|
0.00%
0/7 • Baseline up to 4 Weeks
|
0.00%
0/12 • Baseline up to 4 Weeks
|
0.00%
0/11 • Baseline up to 4 Weeks
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/8 • Baseline up to 4 Weeks
|
0.00%
0/7 • Baseline up to 4 Weeks
|
0.00%
0/12 • Baseline up to 4 Weeks
|
9.1%
1/11 • Number of events 1 • Baseline up to 4 Weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
2/8 • Number of events 2 • Baseline up to 4 Weeks
|
0.00%
0/7 • Baseline up to 4 Weeks
|
8.3%
1/12 • Number of events 1 • Baseline up to 4 Weeks
|
9.1%
1/11 • Number of events 1 • Baseline up to 4 Weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER