Trial Outcomes & Findings for A Study to Evaluate Pharmacokinetics (PK) and Safety of Oral Mobocertinib in Participants With Moderate or Severe Hepatic Impairment (HI) and Normal Hepatic Function (NCT NCT04056468)
NCT ID: NCT04056468
Last Updated: 2023-11-03
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Results posted on
2023-11-03
Participant Flow
Participants took part in the study at 2 investigative sites in the United States from 09 October 2020 to 26 February 2022.
Participants with a diagnosis of moderate or severe hepatic impairment (HI) were enrolled to receive mobocertinib and were compared to a matched-normal hepatic function arm.
Participant milestones
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
Mobocertinib 40 milligram (mg), capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
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
A Study to Evaluate Pharmacokinetics (PK) and Safety of Oral Mobocertinib in Participants With Moderate or Severe Hepatic Impairment (HI) and Normal Hepatic Function
Baseline characteristics by cohort
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
61.1 years
STANDARD_DEVIATION 3.76 • n=5 Participants
|
56.1 years
STANDARD_DEVIATION 8.64 • n=7 Participants
|
59.4 years
STANDARD_DEVIATION 6.09 • n=5 Participants
|
58.9 years
STANDARD_DEVIATION 6.54 • n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
6 Participants
n=4 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
|
|
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
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 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
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 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
|
|
Region of Enrollment
United States
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Weight
|
87.06 kg
STANDARD_DEVIATION 24.847 • n=5 Participants
|
81.46 kg
STANDARD_DEVIATION 14.803 • n=7 Participants
|
85.88 kg
STANDARD_DEVIATION 16.824 • n=5 Participants
|
84.80 kg
STANDARD_DEVIATION 18.622 • n=4 Participants
|
|
Height
|
170.9 cm
STANDARD_DEVIATION 11.72 • n=5 Participants
|
169.4 cm
STANDARD_DEVIATION 9.71 • n=7 Participants
|
167.4 cm
STANDARD_DEVIATION 8.98 • n=5 Participants
|
169.2 cm
STANDARD_DEVIATION 9.86 • n=4 Participants
|
|
Body Mass Index (BMI)
|
29.279 kg/m^2
STANDARD_DEVIATION 4.7428 • n=5 Participants
|
28.378 kg/m^2
STANDARD_DEVIATION 4.5553 • n=7 Participants
|
30.456 kg/m^2
STANDARD_DEVIATION 4.0801 • n=5 Participants
|
29.371 kg/m^2
STANDARD_DEVIATION 4.3571 • n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: Pharmacokinetic (PK) set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
9.67 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 58.2
|
11.3 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 31.7
|
10.5 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 37.6
|
|
Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
3.88 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 28.8
|
2.82 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 27.9
|
4.80 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 23.6
|
|
Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
0.752 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 38.6
|
0.722 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 32.5
|
1.15 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 31.7
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
0.153 ng/mL
Geometric Coefficient of Variation 51.2
|
0.167 ng/mL
Geometric Coefficient of Variation 50.3
|
0.184 ng/mL
Geometric Coefficient of Variation 39.7
|
|
Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
0.0569 ng/mL
Geometric Coefficient of Variation 24.4
|
0.0396 ng/mL
Geometric Coefficient of Variation 35.9
|
0.0729 ng/mL
Geometric Coefficient of Variation 22.2
|
|
Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
0.00518 ng/mL
Geometric Coefficient of Variation 81.3
|
0.00837 ng/mL
Geometric Coefficient of Variation 28.9
|
0.0127 ng/mL
Geometric Coefficient of Variation 36.1
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Number analyzed is the number of participants with data available for analysis for the specified category. Data was not collected for AP32914 as no participant displayed a sufficient PK profile with respect to this parameter.
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
206 nanogram*hours/milliliters (ng*h/mL)
Geometric Coefficient of Variation 32.7
|
291 nanogram*hours/milliliters (ng*h/mL)
Geometric Coefficient of Variation 48.9
|
199 nanogram*hours/milliliters (ng*h/mL)
Geometric Coefficient of Variation 36.2
|
|
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
91.6 nanogram*hours/milliliters (ng*h/mL)
Geometric Coefficient of Variation 22.2
|
115 nanogram*hours/milliliters (ng*h/mL)
Geometric Coefficient of Variation 1.94
|
105 nanogram*hours/milliliters (ng*h/mL)
Geometric Coefficient of Variation 31.5
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Number analyzed is the number of participants with data available for analysis for the specified category. Data was not collected for AP32914 as no participant displayed a sufficient PK profile with respect to this parameter.
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
3.26 ng*h/mL
Geometric Coefficient of Variation 42.6
|
4.31 ng*h/mL
Geometric Coefficient of Variation 42.4
|
3.50 ng*h/mL
Geometric Coefficient of Variation 34.9
|
|
AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
1.32 ng*h/mL
Geometric Coefficient of Variation 28.4
|
1.48 ng*h/mL
Geometric Coefficient of Variation 28.5
|
1.60 ng*h/mL
Geometric Coefficient of Variation 29.3
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
192 ng*h/mL
Geometric Coefficient of Variation 34.2
|
275 ng*h/mL
Geometric Coefficient of Variation 50.3
|
186 ng*h/mL
Geometric Coefficient of Variation 38.7
|
|
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
69.3 ng*h/mL
Geometric Coefficient of Variation 21.3
|
64.5 ng*h/mL
Geometric Coefficient of Variation 52.1
|
91.9 ng*h/mL
Geometric Coefficient of Variation 35.1
|
|
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
7.61 ng*h/mL
Geometric Coefficient of Variation 48.1
|
9.32 ng*h/mL
Geometric Coefficient of Variation 91.4
|
12.5 ng*h/mL
Geometric Coefficient of Variation 71.3
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
3.04 ng*h/mL
Geometric Coefficient of Variation 43.3
|
4.06 ng*h/mL
Geometric Coefficient of Variation 42.9
|
3.28 ng*h/mL
Geometric Coefficient of Variation 36.2
|
|
AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
1.02 ng*h/mL
Geometric Coefficient of Variation 24.9
|
0.906 ng*h/mL
Geometric Coefficient of Variation 42.8
|
1.40 ng*h/mL
Geometric Coefficient of Variation 32.0
|
|
AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
0.0524 ng*h/mL
Geometric Coefficient of Variation 82.5
|
0.108 ng*h/mL
Geometric Coefficient of Variation 45.5
|
0.138 ng*h/mL
Geometric Coefficient of Variation 79.5
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
2.00 hours (h)
Interval 1.0 to 8.0
|
4.00 hours (h)
Interval 1.0 to 8.0
|
6.00 hours (h)
Interval 1.0 to 8.0
|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
2.00 hours (h)
Interval 2.0 to 4.0
|
4.00 hours (h)
Interval 2.0 to 6.0
|
6.00 hours (h)
Interval 2.0 to 6.0
|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
5.00 hours (h)
Interval 2.0 to 8.0
|
4.00 hours (h)
Interval 2.0 to 8.0
|
6.00 hours (h)
Interval 2.0 to 8.0
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Number analyzed is the number of participants with data available for analysis for the specified category. Data was not collected for AP32914 as no participant displayed a sufficient PK profile with respect to this parameter.
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
26.4 hours
Geometric Coefficient of Variation 16.8
|
30.7 hours
Geometric Coefficient of Variation 20.9
|
22.9 hours
Geometric Coefficient of Variation 28.1
|
|
t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
31.7 hours
Geometric Coefficient of Variation 36.2
|
45.0 hours
Geometric Coefficient of Variation 44.9
|
25.9 hours
Geometric Coefficient of Variation 29.1
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Number analyzed is the number of participants with data available for analysis for the specified category. Data was not collected for AP32914 as no participant displayed a sufficient PK profile with respect to this parameter.
Terminal elimination rate constant (λz) is a mathematical estimate calculated using log-linear regression of the terminal portions of a plasma concentration against time curve.
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
λz: Terminal Elimination Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
0.0263 1/hour
Geometric Coefficient of Variation 16.8
|
0.0226 1/hour
Geometric Coefficient of Variation 20.9
|
0.0303 1/hour
Geometric Coefficient of Variation 28.1
|
|
λz: Terminal Elimination Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
0.0218 1/hour
Geometric Coefficient of Variation 36.2
|
0.0154 1/hour
Geometric Coefficient of Variation 44.9
|
0.0268 1/hour
Geometric Coefficient of Variation 29.1
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib
|
195 liters per hour (L/hour)
Geometric Coefficient of Variation 32.7
|
137 liters per hour (L/hour)
Geometric Coefficient of Variation 48.9
|
201 liters per hour (L/hour)
Geometric Coefficient of Variation 36.2
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib
|
12300 L/hour
Geometric Coefficient of Variation 42.6
|
9290 L/hour
Geometric Coefficient of Variation 42.4
|
11400 L/hour
Geometric Coefficient of Variation 34.9
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib
|
7400 liters
Geometric Coefficient of Variation 30.5
|
6090 liters
Geometric Coefficient of Variation 30.7
|
6640 liters
Geometric Coefficient of Variation 37.7
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib
|
467000 liters
Geometric Coefficient of Variation 34.3
|
412000 liters
Geometric Coefficient of Variation 22.6
|
377000 liters
Geometric Coefficient of Variation 24.9
|
SECONDARY outcome
Timeframe: Day 1 at multiple time points (up to 24 hours) post-dosePopulation: PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations).
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
98.4 percentage bound
Standard Deviation 0.385
|
98.5 percentage bound
Standard Deviation 0.397
|
98.2 percentage bound
Standard Deviation 0.426
|
|
Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
98.5 percentage bound
Standard Deviation 0.114
|
98.6 percentage bound
Standard Deviation 0.321
|
98.5 percentage bound
Standard Deviation 0.129
|
|
Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
99.2 percentage bound
Standard Deviation 0.332
|
98.7 percentage bound
Standard Deviation 0.621
|
98.9 percentage bound
Standard Deviation 0.245
|
SECONDARY outcome
Timeframe: Baseline up to 30 days after last dose of study drug (up to Day 32)Population: Safety set included all participants who received the study drug.
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Outcome measures
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 Participants
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
|
1 Participants
|
0 Participants
|
2 Participants
|
Adverse Events
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Severe HI (Child-Pugh C): Mobocertinib 40 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Normal Hepatic Function: Mobocertinib 40 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Moderate HI (Child-Pugh B): Mobocertinib 40 mg
n=8 participants at risk
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Severe HI (Child-Pugh C): Mobocertinib 40 mg
n=8 participants at risk
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
Normal Hepatic Function: Mobocertinib 40 mg
n=8 participants at risk
Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.
|
|---|---|---|---|
|
Gastrointestinal disorders
Dyspepsia
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
0.00%
0/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
0.00%
0/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
0.00%
0/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
0.00%
0/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (up to Day 32)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all participants who received the study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
- Publication restrictions are in place
Restriction type: OTHER