Healthy, Renal Insufficiency
Conditions
Brief summary
The main purpose of this study is to assess the amount of study drug that reaches the bloodstream and the time it takes for the body to get rid of it when given to participants with renal (kidney) impairment compared to healthy participants. The study will last up to 9 days, excluding screening.
Interventions
DRUGSelpercatinib
Administered orally
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
For all participants: * Body mass index (BMI) ≥ 18.0 and ≤ 40.0 kilograms per meter squared (kg/m²) and had a minimum weight of at least 50 kg at screening * Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study * Female of non childbearing potential: must have undergone sterilization procedures at least 6 months prior to the Screening * Males who are capable of fathering a child must agree to use contraception from the time of the dose administration through 6 months after the last dose For renal participants: * Participant has stable renal disease status and function at least 1 month prior to LOXO-292 administration. * Participant is not currently or has not previously being on hemodialysis * Baseline estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease (MDRD) equation at screening as follows: * Severe Renal Impairment (RI): \< 30 milliliter per minute (mL/min)/1.73m² * Moderate RI: ≥ 30 and \< 60 mL/min/1.73m² * Mild RI: ≥ 60 and \< 90 mL/min/1.73m² The MDRD equation is as follows (for females multiply result by 0.742, if African American multiply result by 1.212): eGFR = 175 x \[serum creatinine in milligrams per deciliter (mg/dL) measured with a standardized assay\]\^-1.154 x (Age)\^-0.203
Exclusion criteria
For renal participants: * Has rapidly fluctuating renal function, as determined by historical measurements; or has demonstrated or suspected renal artery stenosis. Rapidly fluctuating renal function is defined as creatinine clearance or eGFR that differs by more than 20% within at least 3 months of the screening creatinine clearance or eGFR. If historical measurements are not available, then the 2 screening measurements will be used to demonstrate stability. * Participants who have had a renal transplant, a nephrectomy, or participants with a known history of nephrotic syndrome. * Participants who have required new medication for renal disease within 30 days prior to Check-in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: AUC0-inf of Selpercatinib |
| Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: AUC0-t of Selpercatinib |
| PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: Percentage of AUC0-inf extrapolated was calculated as (1 - AUC0-t/AUC0-inf) \* 100. |
| PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: Cmax of Selpercatinib |
| PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: Tmax of Selpercatinib |
| PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: Apparent terminal elimination rate constant; represents the fraction of drug eliminated per unit time calculated by linear least squares regression analysis using the maximum number of points in the terminal log linear phase (e.g., three or more non zero plasma concentrations). |
| PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: t½ of Selpercatinib. |
| PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: CL/F of Selpercatinib |
| PK: Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | PK: Vz/F of Selpercatinib |
| PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | AUC0-t,u was calculated by multiplying AUC0-t by Fu (i.e., AUC0-t\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins. |
| PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | AUC0-inf,u was calculated by multiplying AUC0-inf by Fu (i.e., AUC0-inf\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins. |
| PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | Cmax,u was calculated by multiplying Cmax by Fu (i.e., Cmax\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins. |
| PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | CL/F,u was calculated by multiplying CL/F by Fu (i.e., CL/F\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins. |
| PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma | Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | Vz/F,u was calculated by multiplying Vz/F by Fu (i.e., Vz/F\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins. |
| PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine | Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose | PK: CumAe was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome. |
| PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine | Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose | PK: Cum%Dose was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome. |
| PK: Renal Clearance (CLr) of Selpercatinib in Urine | Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose | PK: CLr of Selpercatinib was reported.The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Selpercatinib (Control; Normal Renal Function) Participants with normal renal function (eGFR ≥ 90 mL/min/1.73 m²) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state. | 13 |
| Selpercatinib (Mild Renal Impairment) Participants with mild renal impairment (eGFR between 60 and 90 mL/min/1.73 m²) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state. | 9 |
| Selpercatinib (Moderate Renal Impairment) Participants with moderate renal impairment (eGFR between 30 and 60 mL/min/1.73 m²) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state. | 8 |
| Selpercatinib (Severe Renal Impairment) Participants with severe renal impairment (eGFR \< 30 mL/min/1.73 m² and not requiring hemodialysis) received a single 160 mg oral dose of Selpercatinib on Day 1, administered in a fasted state. | 7 |
| Total | 37 |
Baseline characteristics
| Characteristic | Selpercatinib (Control; Normal Renal Function) | Total | Selpercatinib (Severe Renal Impairment) | Selpercatinib (Moderate Renal Impairment) | Selpercatinib (Mild Renal Impairment) |
|---|---|---|---|---|---|
| Age, Continuous | 59.40 years STANDARD_DEVIATION 6.42 | 60.20 years STANDARD_DEVIATION 6.14 | 61.30 years STANDARD_DEVIATION 5.85 | 62.60 years STANDARD_DEVIATION 6.02 | 58.40 years STANDARD_DEVIATION 6.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 11 Participants | 3 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 26 Participants | 4 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 16 Participants | 2 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 21 Participants | 5 Participants | 4 Participants | 6 Participants |
| Region of Enrollment United States | 13 Participants | 37 Participants | 7 Participants | 8 Participants | 9 Participants |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 2 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 24 Participants | 5 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 9 | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 2 / 13 | 3 / 9 | 3 / 8 | 3 / 7 |
| serious Total, serious adverse events | 0 / 13 | 0 / 9 | 0 / 8 | 0 / 7 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib in Plasma
PK: AUC0-t of Selpercatinib
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib in Plasma | 19770 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 52.1 |
| Selpercatinib (Mild Renal Impairment) | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib in Plasma | 23440 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 36 |
| Selpercatinib (Moderate Renal Impairment) | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib in Plasma | 29270 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25.6 |
| Selpercatinib (Severe Renal Impairment) | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib in Plasma | 20640 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 71 |
Primary
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma
PK: t½ of Selpercatinib.
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma | 24.854 hours (hr) | Standard Deviation 4.085 |
| Selpercatinib (Mild Renal Impairment) | PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma | 22.632 hours (hr) | Standard Deviation 8.7328 |
| Selpercatinib (Moderate Renal Impairment) | PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma | 27.139 hours (hr) | Standard Deviation 7.1091 |
| Selpercatinib (Severe Renal Impairment) | PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma | 33.828 hours (hr) | Standard Deviation 10.4879 |
Primary
PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma
PK: Apparent terminal elimination rate constant; represents the fraction of drug eliminated per unit time calculated by linear least squares regression analysis using the maximum number of points in the terminal log linear phase (e.g., three or more non zero plasma concentrations).
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma | 0.02853 One per hour (1/hour) | Standard Deviation 0.0043443 |
| Selpercatinib (Mild Renal Impairment) | PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma | 0.03434 One per hour (1/hour) | Standard Deviation 0.012429 |
| Selpercatinib (Moderate Renal Impairment) | PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma | 0.02662 One per hour (1/hour) | Standard Deviation 0.0047866 |
| Selpercatinib (Severe Renal Impairment) | PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma | 0.02204 One per hour (1/hour) | Standard Deviation 0.0061504 |
Primary
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib in Plasma
PK: CL/F of Selpercatinib
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib in Plasma | 8.976 Liters per Hour (L/h) | Standard Deviation 4.6533 |
| Selpercatinib (Mild Renal Impairment) | PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib in Plasma | 7.188 Liters per Hour (L/h) | Standard Deviation 2.6117 |
| Selpercatinib (Moderate Renal Impairment) | PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib in Plasma | 5.581 Liters per Hour (L/h) | Standard Deviation 1.3807 |
| Selpercatinib (Severe Renal Impairment) | PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib in Plasma | 9.184 Liters per Hour (L/h) | Standard Deviation 6.5822 |
Primary
PK: Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Selpercatinib in Plasma
PK: Vz/F of Selpercatinib
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Selpercatinib in Plasma | 334.5 Liter | Standard Deviation 225.17 |
| Selpercatinib (Mild Renal Impairment) | PK: Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Selpercatinib in Plasma | 227.9 Liter | Standard Deviation 106.14 |
| Selpercatinib (Moderate Renal Impairment) | PK: Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Selpercatinib in Plasma | 219.4 Liter | Standard Deviation 82.255 |
| Selpercatinib (Severe Renal Impairment) | PK: Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Selpercatinib in Plasma | 444.7 Liter | Standard Deviation 309.92 |
Primary
PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma
PK: AUC0-inf of Selpercatinib
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma | 19870 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 52 |
| Selpercatinib (Mild Renal Impairment) | PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma | 23510 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 36 |
| Selpercatinib (Moderate Renal Impairment) | PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma | 29470 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25.8 |
| Selpercatinib (Severe Renal Impairment) | PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma | 21000 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 71.4 |
Primary
PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine
PK: CumAe was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.
Time frame: Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine | 16.14 milligram (mg) | Standard Deviation 9.5297 |
| Selpercatinib (Mild Renal Impairment) | PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine | 14.54 milligram (mg) | Standard Deviation 3.1611 |
| Selpercatinib (Moderate Renal Impairment) | PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine | 13.94 milligram (mg) | Standard Deviation 5.3203 |
| Selpercatinib (Severe Renal Impairment) | PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine | 7.652 milligram (mg) | Standard Deviation 5.421 |
Primary
PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine
PK: Cum%Dose was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.
Time frame: Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine | 10.09 percentage of dose excreted | Standard Deviation 5.956 |
| Selpercatinib (Mild Renal Impairment) | PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine | 9.087 percentage of dose excreted | Standard Deviation 1.9757 |
| Selpercatinib (Moderate Renal Impairment) | PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine | 8.713 percentage of dose excreted | Standard Deviation 3.3252 |
| Selpercatinib (Severe Renal Impairment) | PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine | 4.782 percentage of dose excreted | Standard Deviation 3.3881 |
Primary
PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma
PK: Cmax of Selpercatinib
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma | 1399 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 107.3 |
| Selpercatinib (Mild Renal Impairment) | PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma | 2247 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22.3 |
| Selpercatinib (Moderate Renal Impairment) | PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma | 1742 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25.1 |
| Selpercatinib (Severe Renal Impairment) | PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma | 1006 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 159.6 |
Primary
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma
PK: Percentage of AUC0-inf extrapolated was calculated as (1 - AUC0-t/AUC0-inf) \* 100.
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma | 0.4856 percentage of AUCextrap | Standard Deviation 0.12819 |
| Selpercatinib (Mild Renal Impairment) | PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma | 0.2988 percentage of AUCextrap | Standard Deviation 0.10713 |
| Selpercatinib (Moderate Renal Impairment) | PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma | 0.6738 percentage of AUCextrap | Standard Deviation 0.33398 |
| Selpercatinib (Severe Renal Impairment) | PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma | 1.706 percentage of AUCextrap | Standard Deviation 1.5917 |
Primary
PK: Renal Clearance (CLr) of Selpercatinib in Urine
PK: CLr of Selpercatinib was reported.The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.
Time frame: Predose (spot collection), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Renal Clearance (CLr) of Selpercatinib in Urine | 735.9 milliliter per hour (mL/hr) | Standard Deviation 230.39 |
| Selpercatinib (Mild Renal Impairment) | PK: Renal Clearance (CLr) of Selpercatinib in Urine | 641.6 milliliter per hour (mL/hr) | Standard Deviation 243.96 |
| Selpercatinib (Moderate Renal Impairment) | PK: Renal Clearance (CLr) of Selpercatinib in Urine | 480.4 milliliter per hour (mL/hr) | Standard Deviation 208.23 |
| Selpercatinib (Severe Renal Impairment) | PK: Renal Clearance (CLr) of Selpercatinib in Urine | 314.6 milliliter per hour (mL/hr) | Standard Deviation 94.084 |
Primary
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma
PK: Tmax of Selpercatinib
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma | 1.500 hours (hr) |
| Selpercatinib (Mild Renal Impairment) | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma | 1.500 hours (hr) |
| Selpercatinib (Moderate Renal Impairment) | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma | 1.500 hours (hr) |
| Selpercatinib (Severe Renal Impairment) | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma | 1.000 hours (hr) |
Primary
PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma
AUC0-inf,u was calculated by multiplying AUC0-inf by Fu (i.e., AUC0-inf\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma | 535.7 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54.3 |
| Selpercatinib (Mild Renal Impairment) | PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma | 661.6 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24.4 |
| Selpercatinib (Moderate Renal Impairment) | PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma | 862.1 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28.1 |
| Selpercatinib (Severe Renal Impairment) | PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma | 722.3 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 93.9 |
Primary
PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma
AUC0-t,u was calculated by multiplying AUC0-t by Fu (i.e., AUC0-t\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma | 533.1 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54.3 |
| Selpercatinib (Mild Renal Impairment) | PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma | 659.7 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24.4 |
| Selpercatinib (Moderate Renal Impairment) | PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma | 856.3 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| Selpercatinib (Severe Renal Impairment) | PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma | 709.9 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 93 |
Primary
PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma
CL/F,u was calculated by multiplying CL/F by Fu (i.e., CL/F\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma | 337.9 Liters per Hour (L/h) | Standard Deviation 194.45 |
| Selpercatinib (Mild Renal Impairment) | PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma | 247.9 Liters per Hour (L/h) | Standard Deviation 58.03 |
| Selpercatinib (Moderate Renal Impairment) | PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma | 191.6 Liters per Hour (L/h) | Standard Deviation 49.277 |
| Selpercatinib (Severe Renal Impairment) | PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma | 300.6 Liters per Hour (L/h) | Standard Deviation 294.31 |
Primary
PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma
Cmax,u was calculated by multiplying Cmax by Fu (i.e., Cmax\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma | 37.72 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 113.6 |
| Selpercatinib (Mild Renal Impairment) | PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma | 63.23 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23.4 |
| Selpercatinib (Moderate Renal Impairment) | PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma | 50.95 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28.5 |
| Selpercatinib (Severe Renal Impairment) | PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma | 34.60 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 187.8 |
Primary
PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma
Vz/F,u was calculated by multiplying Vz/F by Fu (i.e., Vz/F\*Fu). Fu represented the unbound fraction of Selpercatinib in plasma, that is, the portion of the drug not bound to plasma proteins.
Time frame: Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All enrolled participants who received at least one dose of the study drug and had evaluable PK data. Participants were excluded from the analysis if they experienced emesis (vomiting) that occurred at or before 2 times the median Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selpercatinib (Control; Normal Renal Function) | PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma | 12700 Liter (L) | Standard Deviation 9498.5 |
| Selpercatinib (Mild Renal Impairment) | PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma | 8214 Liter (L) | Standard Deviation 4487.5 |
| Selpercatinib (Moderate Renal Impairment) | PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma | 7697 Liter (L) | Standard Deviation 3676.1 |
| Selpercatinib (Severe Renal Impairment) | PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma | 14340 Liter (L) | Standard Deviation 12842 |