Healthy Volunteers, Renal Impairment
Conditions
Keywords
Drug Therapy
Brief summary
It is hoped that mobocertinib will eventually help people with cancer with severely reduced kidney function. The main aim of this study is to learn about the levels of mobocertinib in the blood and urine of participants with severely reduced kidney function and participants with healthy kidneys. These participants do not have cancer. The information from this study will be used to work out the best dose of mobocertinib for people with cancer with severely reduced kidney function in the future. At the first visit, the study doctor will check who can take part. Participants who can take part will be placed into 1 of 2 treatment groups. Participants with severely reduced kidney function will be in 1 group. Participants with healthy kidneys will be in the other group. Participants in both groups will receive the same treatment and the group results will be compared. Participants from both groups will take 1 capsule of mobocertinib. They will stay in the clinic for 10 days so the study doctors can check the amount of mobocertinib in the blood and urine of these participants over time. The study doctors will also check if the participants have any side effects from this treatment. The clinic will call the participants 30 days after they took mobocertinib to check if they have any more side effects from their treatment.
Detailed description
The drug being tested in this study is called mobocertinib. This study is to assess the pharmacokinetic (PK) of mobocertinib and its active metabolites (AP32960 and AP32914) in participants with severe RI compared to matched-healthy participants with normal renal function. The study will enroll approximately 24 participants. Participants will be assigned to 1 of the following 2 treatment groups: * Severe RI: Mobocertinib 80 mg * Normal Renal Function: Mobocertinib 80 mg Healthy participants with normal renal function will be recruited to match severe RI by age (mean plus or minus \[+-\] 10 years), gender (+-2 participants per gender), and body mass index (BMI), (mean +- 10 percent \[%\]). All participants will be asked to take single dose of mobocertinib on Day 1. This multi-center trial will be conducted in the United States. The overall time to participate in this study is 51 days. Participants will be contacted by telephone 30 days after the last dose of study drug for a follow-up assessment.
Interventions
DRUGMobocertinib
Mobocertinib capsule.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 81 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria for Healthy Participants: 1. Continuous non-smoker or moderate smoker (less than or equal to \[\<=\] 10 cigarettes/day or the equivalent) before screening. Participant must agree to consume no more than 5 cigarettes or equivalent/day from the 7 days prior to mobocertinib dosing and throughout the period of PK sample collection. 2. Body mass index (BMI) greater than or equal to (\>=) 18.0 and \<=39.0 kilogram per square meter (kg/m\^2), at screening. Participants will be matched to RI participants by BMI (mean +- 10%) at screening. At least 50% of the participants will be required to be of BMI \>=18.0 and \<=35.0 kg/m\^2, at screening. 3. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the Investigator or designee. Has liver function tests including alanine aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline phosphatase (ALP), and total bilirubin within the upper limit of normal at screening and at check-in. 4. Baseline estimated glomerular filtration rate (eGFR) \>=90 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) based on the Modification of Diet in Renal Disease (MDRD) equation at screening divided by standard body surface area (BSA) value of 1.73 m\^2. For participants with non-standard BSA, the eGFR value calculated by MDRD formula will be multiplied by the individual's BSA calculated using appropriate formula and divided by 1.73 m\^2. Inclusion Criteria for Participants with RI: 1. Continuous non-smoker or moderate smoker (\<=10 cigarettes/day or the equivalent) before screening. Participant must agree to consume no more than 5 cigarettes or equivalent/day from the 7 days prior to dose of mobocertinib and throughout the period of PK sample collection. 2. BMI \>=18.0 and \<=39.0 kg/m\^2, at screening. At least 50% of the participants will be required to be of BMI \>=18.0 and \<=35.0 kg/m\^2, at screening. 3. Aside from RI, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, ECGs, and screening clinical laboratory profiles, as deemed by the Investigator or designee. 4. Baseline eGFR 15-29 milliliter (mL) not on dialysis based on the MDRD equation at screening divided by standard BSA value of 1.73 m\^2. For participants with non-standard BSA, the eGFR value calculated by MDRD formula will be multiplied by the individual's BSA calculated using appropriate formula and divided by 1.73 m\^2. 5. Has a diagnosis of chronic (greater than \[\>\] 6 months), stable (no significant changes in renal function \[less than \[\<\] 30%\] in the 30 days preceding screening; no acute episodes of illness within the previous 2 months due to deterioration in renal function) renal insufficiency. Participants with RI may have related medical conditions consistent with their disease (example, mild diabetes) that are stable for at least 3 months prior to screening, in the opinion of the Investigator or designee.
Exclusion criteria
1. Positive results at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). 2. Positive test result for coronavirus disease 2019 (COVID-19) testing at screening or check-in. 3. Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening. 4. Seated blood pressure is less than 90/40 millimeters of mercury (mmHg) or greater than 180/100 mmHg at screening. 5. Healthy participants: QT interval with Fridericia's correction (QTcF) interval is \>=450 millisecond (msec) in males or \>=470 msec in females or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening 6. RI participants: QTcF interval is \>500 msec or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening. 7. Unable to refrain from or anticipates the use of any medication or substance (including prescription or over-the-counter, vitamin supplements, natural or herbal supplements) as indicated in (Prohibitions and Concomitant Medication) for the prohibited time period. 8. Been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to dosing and throughout the study. 9. Donation of blood or significant blood loss within 56 days prior to dosing. 10. Plasma donation within 7 days prior to dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose | — |
| CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine | Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose | — |
| Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine | Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose | — |
| Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| AUCinf,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| 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) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| 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) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| Combined Molar Cmax,u: Combined Molar Unbound Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| Combined Molar AUClast,u: Combined Molar Unbound AUClast for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| Combined Molar AUCinf,u: Combined Molar Unbound AUCinf for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | 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. |
| CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
| Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib | Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to end of study (EOS) (up to 40 days) | 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. |
| Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Day 1 at multiple time points (up to 24 hours) post-dose | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 3 investigative sites in the United States from 04 March 2020 to 20 April 2022.
Pre-assignment details
Participants with severe renal impairment or normal renal function were enrolled in this study to receive a single dose of 80 mg of mobocertinib.
Participants by arm
| Arm | Count |
|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1. | 14 |
| Normal Renal Function: Mobocertinib 80 mg Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1. | 12 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Severe Renal Impairment: Mobocertinib 80 mg | Total | Normal Renal Function: Mobocertinib 80 mg |
|---|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 11.86 | 61.7 years STANDARD_DEVIATION 9.07 | 59.7 years STANDARD_DEVIATION 3.55 |
| Body Mass Index (BMI) | 30.896 kg/m^2 STANDARD_DEVIATION 4.5466 | 30.532 kg/m^2 STANDARD_DEVIATION 3.4508 | 30.108 kg/m^2 STANDARD_DEVIATION 1.5066 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 16 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 165.1 cm STANDARD_DEVIATION 6.53 | 168.1 cm STANDARD_DEVIATION 7.1 | 171.5 cm STANDARD_DEVIATION 6.32 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 14 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 12 Participants | 5 Participants |
| Region of Enrollment United States | 14 Participants | 26 Participants | 12 Participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 10 Participants | 17 Participants | 7 Participants |
| Weight | 84.30 kg STANDARD_DEVIATION 13.712 | 86.30 kg STANDARD_DEVIATION 11.143 | 88.63 kg STANDARD_DEVIATION 6.997 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 12 |
| other Total, other adverse events | 5 / 14 | 0 / 12 |
| serious Total, serious adverse events | 1 / 14 | 0 / 12 |
Outcome results
Primary
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 255 ng*hours(hr)/mL | Geometric Coefficient of Variation 58.1 |
| Normal Renal Function: Mobocertinib 80 mg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 184 ng*hours(hr)/mL | Geometric Coefficient of Variation 36.7 |
| Normal Renal Function: Mobocertinib 80 mg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 42.3 ng*hours(hr)/mL | Geometric Coefficient of Variation 33.2 |
Primary
AUCinf,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 3.16 ng*hr/mL | Geometric Coefficient of Variation 91.9 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 2.15 ng*hr/mL | Geometric Coefficient of Variation 56.6 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 0.461 ng*hr/mL | Geometric Coefficient of Variation 67.3 |
Primary
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)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 219 ng*hr/mL | Geometric Coefficient of Variation 70.3 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 159 ng*hr/mL | Geometric Coefficient of Variation 42.4 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 18.7 ng*hr/mL | Geometric Coefficient of Variation 75 |
Primary
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)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 0.172 ng*hr/mL | Geometric Coefficient of Variation 132 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 2.68 ng*hr/mL | Geometric Coefficient of Variation 105 |
| Normal Renal Function: Mobocertinib 80 mg | 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 | 1.82 ng*hr/mL | Geometric Coefficient of Variation 63.5 |
Primary
CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib | 111 Liters per hour (L/hr) | Geometric Coefficient of Variation 97.8 |
| Normal Renal Function: Mobocertinib 80 mg | CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib | 314 Liters per hour (L/hr) | Geometric Coefficient of Variation 58.1 |
Primary
CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 0.694 L/hr | Standard Deviation 0.827 |
| Severe Renal Impairment: Mobocertinib 80 mg | CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 0.373 L/hr | Standard Deviation 0.172 |
| Severe Renal Impairment: Mobocertinib 80 mg | CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 0.683 L/hr | Standard Deviation 0.427 |
| Normal Renal Function: Mobocertinib 80 mg | CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 1.78 L/hr | Standard Deviation 1.57 |
| Normal Renal Function: Mobocertinib 80 mg | CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 1.77 L/hr | Standard Deviation 0.848 |
| Normal Renal Function: Mobocertinib 80 mg | CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 3.11 L/hr | Standard Deviation 1.42 |
Primary
CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib | 10500 L/hr | Geometric Coefficient of Variation 77.4 |
| Normal Renal Function: Mobocertinib 80 mg | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib | 25300 L/hr | Geometric Coefficient of Variation 91.9 |
Primary
Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 11.2 nanograms per milliliter(ng/mL) | Geometric Coefficient of Variation 69.8 |
| Normal Renal Function: Mobocertinib 80 mg | Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 7.92 nanograms per milliliter(ng/mL) | Geometric Coefficient of Variation 45.8 |
| Normal Renal Function: Mobocertinib 80 mg | Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 1.51 nanograms per milliliter(ng/mL) | Geometric Coefficient of Variation 45.4 |
Primary
Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 0.137 ng/mL | Geometric Coefficient of Variation 106 |
| Normal Renal Function: Mobocertinib 80 mg | Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 0.0904 ng/mL | Geometric Coefficient of Variation 63.9 |
| Normal Renal Function: Mobocertinib 80 mg | Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 0.0144 ng/mL | Geometric Coefficient of Variation 82.7 |
Primary
Combined Molar AUCinf,u: Combined Molar Unbound AUCinf for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | Combined Molar AUCinf,u: Combined Molar Unbound AUCinf for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | 16.8 nM*hr | Geometric Coefficient of Variation 36.7 |
Primary
Combined Molar AUClast,u: Combined Molar Unbound AUClast for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | Combined Molar AUClast,u: Combined Molar Unbound AUClast for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | 8.14 nanomolar*hour(nM*hr) | Geometric Coefficient of Variation 86.2 |
Primary
Combined Molar Cmax,u: Combined Molar Unbound Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | Combined Molar Cmax,u: Combined Molar Unbound Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | 0.419 nanomolar (nM) | Geometric Coefficient of Variation 85.2 |
Primary
CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine
Time frame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine | Mobocertinib | 0.357 milligrams (mg) | Standard Deviation 0.2 |
| Normal Renal Function: Mobocertinib 80 mg | CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine | AP32960 | 0.296 milligrams (mg) | Standard Deviation 0.129 |
| Normal Renal Function: Mobocertinib 80 mg | CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine | AP32914 | 0.0895 milligrams (mg) | Standard Deviation 0.0361 |
Primary
Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine
Time frame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine | 0.339 percentage of dose | Standard Deviation 0.269 |
| Normal Renal Function: Mobocertinib 80 mg | Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine | 0.446 percentage of dose | Standard Deviation 0.251 |
Primary
t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 23.2 hr | Geometric Coefficient of Variation 24.3 |
| Normal Renal Function: Mobocertinib 80 mg | t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 31.7 hr | Geometric Coefficient of Variation 23.3 |
| Normal Renal Function: Mobocertinib 80 mg | t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 14.6 hr | Geometric Coefficient of Variation 37.8 |
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 6.00 hours (hr) |
| Severe Renal Impairment: Mobocertinib 80 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 4.00 hours (hr) |
| Severe Renal Impairment: Mobocertinib 80 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 6.00 hours (hr) |
| Normal Renal Function: Mobocertinib 80 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 6.00 hours (hr) |
| Normal Renal Function: Mobocertinib 80 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 6.00 hours (hr) |
| Normal Renal Function: Mobocertinib 80 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 6.00 hours (hr) |
Primary
Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib | 4480 Liters (L) | Geometric Coefficient of Variation 85 |
| Normal Renal Function: Mobocertinib 80 mg | Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib | 10500 Liters (L) | Geometric Coefficient of Variation 48.4 |
Primary
Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib | 847000 Liters (L) | Geometric Coefficient of Variation 87.7 |
Primary
λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
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.
Time frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Severe Renal Impairment: Mobocertinib 80 mg | 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 |
| Normal Renal Function: Mobocertinib 80 mg | λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 0.0299 per hour (1/hr) | Geometric Coefficient of Variation 24.3 |
| Normal Renal Function: Mobocertinib 80 mg | λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 0.0219 per hour (1/hr) | Geometric Coefficient of Variation 23.3 |
| Normal Renal Function: Mobocertinib 80 mg | λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 0.0475 per hour (1/hr) | Geometric Coefficient of Variation 37.8 |
Secondary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Normal Renal Function: Mobocertinib 80 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
Secondary
Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time frame: Day 1 at multiple time points (up to 24 hours) post-dose
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Renal Impairment: Mobocertinib 80 mg | Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 98.8 percentage bound | Standard Deviation 0.287 |
| Severe Renal Impairment: Mobocertinib 80 mg | Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 98.7 percentage bound | Standard Deviation 0.402 |
| Severe Renal Impairment: Mobocertinib 80 mg | Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 99.3 percentage bound | Standard Deviation 0.469 |
| Normal Renal Function: Mobocertinib 80 mg | Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | Mobocertinib | 98.7 percentage bound | Standard Deviation 0.42 |
| Normal Renal Function: Mobocertinib 80 mg | Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32960 | 98.8 percentage bound | Standard Deviation 0.401 |
| Normal Renal Function: Mobocertinib 80 mg | Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) | AP32914 | 99.2 percentage bound | Standard Deviation 0.524 |