Trial Outcomes & Findings for A Study of Mobocertinib Capsules in People With Severe Kidney Problems and People With Healthy Kidneys (NCT NCT04056455)
NCT ID: NCT04056455
Last Updated: 2024-01-08
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Results posted on
2024-01-08
Participant Flow
Participants took part in the study at 3 investigative sites in the United States from 04 March 2020 to 20 April 2022.
Participants with severe renal impairment or normal renal function were enrolled in this study to receive a single dose of 80 mg of mobocertinib.
Participant milestones
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
12
|
|
Overall Study
Safety Analysis Set
|
14
|
12
|
|
Overall Study
Pharmacokinetic (PK) Analysis Set
|
13
|
12
|
|
Overall Study
COMPLETED
|
13
|
12
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
A Study of Mobocertinib Capsules in People With Severe Kidney Problems and People With Healthy Kidneys
Baseline characteristics by cohort
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=14 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.4 years
STANDARD_DEVIATION 11.86 • n=39 Participants
|
59.7 years
STANDARD_DEVIATION 3.55 • n=41 Participants
|
61.7 years
STANDARD_DEVIATION 9.07 • n=35 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
9 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=39 Participants
|
7 Participants
n=41 Participants
|
17 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
10 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
16 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=39 Participants
|
7 Participants
n=41 Participants
|
14 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
12 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Region of Enrollment
United States
|
14 Participants
n=39 Participants
|
12 Participants
n=41 Participants
|
26 Participants
n=35 Participants
|
|
Height
|
165.1 cm
STANDARD_DEVIATION 6.53 • n=39 Participants
|
171.5 cm
STANDARD_DEVIATION 6.32 • n=41 Participants
|
168.1 cm
STANDARD_DEVIATION 7.10 • n=35 Participants
|
|
Weight
|
84.30 kg
STANDARD_DEVIATION 13.712 • n=39 Participants
|
88.63 kg
STANDARD_DEVIATION 6.997 • n=41 Participants
|
86.30 kg
STANDARD_DEVIATION 11.143 • n=35 Participants
|
|
Body Mass Index (BMI)
|
30.896 kg/m^2
STANDARD_DEVIATION 4.5466 • n=39 Participants
|
30.108 kg/m^2
STANDARD_DEVIATION 1.5066 • n=41 Participants
|
30.532 kg/m^2
STANDARD_DEVIATION 3.4508 • n=35 Participants
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
17.1 nanograms per milliliter(ng/mL)
Geometric Coefficient of Variation 326
|
11.2 nanograms per milliliter(ng/mL)
Geometric Coefficient of Variation 69.8
|
|
Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
12.2 nanograms per milliliter(ng/mL)
Geometric Coefficient of Variation 51.4
|
7.92 nanograms per milliliter(ng/mL)
Geometric Coefficient of Variation 45.8
|
|
Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
2.24 nanograms per milliliter(ng/mL)
Geometric Coefficient of Variation 73.9
|
1.51 nanograms per milliliter(ng/mL)
Geometric Coefficient of Variation 45.4
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
0.188 ng/mL
Geometric Coefficient of Variation 252
|
0.137 ng/mL
Geometric Coefficient of Variation 106
|
|
Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
0.149 ng/mL
Geometric Coefficient of Variation 53.7
|
0.0904 ng/mL
Geometric Coefficient of Variation 63.9
|
|
Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
0.0112 ng/mL
Geometric Coefficient of Variation 108
|
0.0144 ng/mL
Geometric Coefficient of Variation 82.7
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02. Number analyzed is the number of participants with data available for analysis for the specific category.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=11 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
720 ng*hours(hr)/mL
Geometric Coefficient of Variation 97.8
|
255 ng*hours(hr)/mL
Geometric Coefficient of Variation 58.1
|
|
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
328 ng*hours(hr)/mL
Geometric Coefficient of Variation 43.6
|
184 ng*hours(hr)/mL
Geometric Coefficient of Variation 36.7
|
|
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
93.6 ng*hours(hr)/mL
Geometric Coefficient of Variation 73.6
|
42.3 ng*hours(hr)/mL
Geometric Coefficient of Variation 33.2
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02. Number analyzed is the number of participants with data available for analysis for the specific category.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=11 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
AUCinf,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
7.61 ng*hr/mL
Geometric Coefficient of Variation 77.4
|
3.16 ng*hr/mL
Geometric Coefficient of Variation 91.9
|
|
AUCinf,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
4.00 ng*hr/mL
Geometric Coefficient of Variation 53.2
|
2.15 ng*hr/mL
Geometric Coefficient of Variation 56.6
|
|
AUCinf,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
0.469 ng*hr/mL
Geometric Coefficient of Variation 134
|
0.461 ng*hr/mL
Geometric Coefficient of Variation 67.3
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, 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
|
463 ng*hr/mL
Geometric Coefficient of Variation 184
|
219 ng*hr/mL
Geometric Coefficient of Variation 70.3
|
|
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
|
305 ng*hr/mL
Geometric Coefficient of Variation 44.4
|
159 ng*hr/mL
Geometric Coefficient of Variation 42.4
|
|
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
|
43.8 ng*hr/mL
Geometric Coefficient of Variation 124
|
18.7 ng*hr/mL
Geometric Coefficient of Variation 75.0
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, 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
|
5.10 ng*hr/mL
Geometric Coefficient of Variation 145
|
2.68 ng*hr/mL
Geometric Coefficient of Variation 105
|
|
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
|
3.72 ng*hr/mL
Geometric Coefficient of Variation 53.7
|
1.82 ng*hr/mL
Geometric Coefficient of Variation 63.5
|
|
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
|
0.219 ng*hr/mL
Geometric Coefficient of Variation 140
|
0.172 ng*hr/mL
Geometric Coefficient of Variation 132
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Combined Molar Cmax,u: Combined Molar Unbound Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
|
0.708 nanomolar (nM)
Geometric Coefficient of Variation 83.7
|
0.419 nanomolar (nM)
Geometric Coefficient of Variation 85.2
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Combined Molar AUClast,u: Combined Molar Unbound AUClast for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
|
16.9 nanomolar*hour(nM*hr)
Geometric Coefficient of Variation 79.5
|
8.14 nanomolar*hour(nM*hr)
Geometric Coefficient of Variation 86.2
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=6 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=5 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Combined Molar AUCinf,u: Combined Molar Unbound AUCinf for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
|
30.1 nM*hr
Geometric Coefficient of Variation 49.0
|
16.8 nM*hr
Geometric Coefficient of Variation 36.7
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
6.00 hours (hr)
Interval 2.0 to 96.0
|
6.00 hours (hr)
Interval 4.0 to 8.0
|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
4.00 hours (hr)
Interval 2.0 to 12.0
|
6.00 hours (hr)
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
|
6.00 hours (hr)
Interval 2.0 to 12.0
|
6.00 hours (hr)
Interval 4.0 to 8.0
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02. Number analyzed is the number of participants with data available for analysis for the specific category.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=11 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
28.0 hr
Geometric Coefficient of Variation 41.5
|
23.2 hr
Geometric Coefficient of Variation 24.3
|
|
t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
40.1 hr
Geometric Coefficient of Variation 38.7
|
31.7 hr
Geometric Coefficient of Variation 23.3
|
|
t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
20.6 hr
Geometric Coefficient of Variation 58.0
|
14.6 hr
Geometric Coefficient of Variation 37.8
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02. Number analyzed is the number of participants with data available for analysis for the specific category.
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 |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=11 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
0.0248 per hour (1/hr)
Geometric Coefficient of Variation 41.5
|
0.0299 per hour (1/hr)
Geometric Coefficient of Variation 24.3
|
|
λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
0.0173 per hour (1/hr)
Geometric Coefficient of Variation 38.7
|
0.0219 per hour (1/hr)
Geometric Coefficient of Variation 23.3
|
|
λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
0.0336 per hour (1/hr)
Geometric Coefficient of Variation 58.0
|
0.0475 per hour (1/hr)
Geometric Coefficient of Variation 37.8
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02 and for whom the terminal disposition phase could be characterized.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=10 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=11 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib
|
111 Liters per hour (L/hr)
Geometric Coefficient of Variation 97.8
|
314 Liters per hour (L/hr)
Geometric Coefficient of Variation 58.1
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02 and for whom the terminal disposition phase of total plasma mobocertinib could be characterized.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=10 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=11 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib
|
10500 L/hr
Geometric Coefficient of Variation 77.4
|
25300 L/hr
Geometric Coefficient of Variation 91.9
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02 and for whom the terminal disposition phase could be characterized.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=10 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=11 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib
|
4480 Liters (L)
Geometric Coefficient of Variation 85.0
|
10500 Liters (L)
Geometric Coefficient of Variation 48.4
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02 and for whom the terminal disposition phase could be characterized.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=10 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=11 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib
|
424000 Liters (L)
Geometric Coefficient of Variation 61.5
|
847000 Liters (L)
Geometric Coefficient of Variation 87.7
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine
Mobocertinib
|
0.271 milligrams (mg)
Standard Deviation 0.216
|
0.357 milligrams (mg)
Standard Deviation 0.200
|
|
CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine
AP32960
|
0.108 milligrams (mg)
Standard Deviation 0.0457
|
0.296 milligrams (mg)
Standard Deviation 0.129
|
|
CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine
AP32914
|
0.0360 milligrams (mg)
Standard Deviation 0.0246
|
0.0895 milligrams (mg)
Standard Deviation 0.0361
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine
|
0.339 percentage of dose
Standard Deviation 0.269
|
0.446 percentage of dose
Standard Deviation 0.251
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Overall number analyzed is the number of participants eligible for descriptive statistical analysis as per criteria specified in Protocol Amendment 02.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=12 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
0.694 L/hr
Standard Deviation 0.827
|
1.78 L/hr
Standard Deviation 1.57
|
|
CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
0.373 L/hr
Standard Deviation 0.172
|
1.77 L/hr
Standard Deviation 0.848
|
|
CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
0.683 L/hr
Standard Deviation 0.427
|
3.11 L/hr
Standard Deviation 1.42
|
SECONDARY outcome
Timeframe: Day 1 at multiple time points (up to 24 hours) post-dosePopulation: PK Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Number analyzed is the number of participants with data available for analysis for the specific category.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=13 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32960
|
98.7 percentage bound
Standard Deviation 0.402
|
98.8 percentage bound
Standard Deviation 0.401
|
|
Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Mobocertinib
|
98.8 percentage bound
Standard Deviation 0.287
|
98.7 percentage bound
Standard Deviation 0.420
|
|
Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
AP32914
|
99.3 percentage bound
Standard Deviation 0.469
|
99.2 percentage bound
Standard Deviation 0.524
|
SECONDARY outcome
Timeframe: From first dose of study drug up to end of study (EOS) (up to 40 days)Population: Safety Analysis Set included all participants who received the dose of study drug.
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, 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 Treatment-emergent Adverse Event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Outcome measures
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=14 Participants
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 Participants
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
|
5 Participants
|
0 Participants
|
Adverse Events
Severe Renal Impairment: Mobocertinib 80 mg
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Normal Renal Function: Mobocertinib 80 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=14 participants at risk
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 participants at risk
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
|
Cardiac disorders
Atrial fibrillation
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
|
Vascular disorders
Hypotension
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
Other adverse events
| Measure |
Severe Renal Impairment: Mobocertinib 80 mg
n=14 participants at risk
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
Normal Renal Function: Mobocertinib 80 mg
n=12 participants at risk
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Gout
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
|
Vascular disorders
Hypertension
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
1/14 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of study drug.
|
0.00%
0/12 • From first dose of study drug up to EOS (up to 40 days)
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 Analysis Set included all participants who received the dose of 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