Trial Outcomes & Findings for A Study of Effect of Selpercatinib (LY3527723) in Participants With Normal and Impaired Renal Function (NCT NCT05469100)

Results Overview

PK: AUC0-t of Selpercatinib

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

37 participants

Primary outcome timeframe

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

Results posted on

2025-09-18

Participant Flow

Participant milestones

Participant milestones
Measure	Selpercatinib (Control; Normal Renal Function) Participants with normal renal function (estimated glomerular filtration rate greater than or equal to \[eGFR ≥ 90 milliliters per minute (mL/min) per 1.73 square meters (m²)\] received a single 160 milligrams (mg) oral dose of Selpercatinib on Day 1, administered in a fasted state.	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.	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.	Selpercatinib (Severe Renal Impairment) Participants with severe renal impairment (eGFR less than (\<) 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.
Overall Study STARTED	13	9	8	7
Overall Study Received at Least One Dose of Selpercatinib	13	9	8	7
Overall Study COMPLETED	13	9	8	7
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Effect of Selpercatinib (LY3527723) in Participants With Normal and Impaired Renal Function

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Selpercatinib (Control; Normal Renal Function) n=13 Participants 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.	Selpercatinib (Mild Renal Impairment) n=9 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.	Total n=37 Participants Total of all reporting groups
Age, Continuous	59.40 years STANDARD_DEVIATION 6.42 • n=5 Participants	58.40 years STANDARD_DEVIATION 6.23 • n=7 Participants	62.60 years STANDARD_DEVIATION 6.02 • n=5 Participants	61.30 years STANDARD_DEVIATION 5.85 • n=4 Participants	60.20 years STANDARD_DEVIATION 6.14 • n=21 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	24 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	11 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	4 Participants n=4 Participants	26 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	16 Participants n=21 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	21 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	13 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	37 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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).

PK: AUC0-t of Selpercatinib

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 52.1	23440 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 36.0	29270 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 25.6	20640 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 71.0

PRIMARY outcome

Timeframe: 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.

PK: AUC0-inf of Selpercatinib

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib in Plasma	19870 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 52.0	23510 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 36.0	29470 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 25.8	21000 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 71.4

PRIMARY outcome

Timeframe: 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.

PK: Percentage of AUC0-inf extrapolated was calculated as (1 - AUC0-t/AUC0-inf) \* 100.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib.in Plasma	0.4856 percentage of AUCextrap Standard Deviation 0.12819	0.2988 percentage of AUCextrap Standard Deviation 0.10713	0.6738 percentage of AUCextrap Standard Deviation 0.33398	1.706 percentage of AUCextrap Standard Deviation 1.5917

PRIMARY outcome

Timeframe: 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.

PK: Cmax of Selpercatinib

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Maximum Observed Concentration (Cmax) of Selpercatinib in Plasma	1399 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 107.3	2247 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 22.3	1742 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 25.1	1006 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 159.6

PRIMARY outcome

Timeframe: 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.

PK: Tmax of Selpercatinib

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Selpercatinib in Plasma	1.500 hours (hr) Interval 1.0 to 24.0	1.500 hours (hr) Interval 1.5 to 2.0	1.500 hours (hr) Interval 1.0 to 3.0	1.000 hours (hr) Interval 0.5 to 24.0

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib in Plasma	0.02853 One per hour (1/hour) Standard Deviation 0.0043443	0.03434 One per hour (1/hour) Standard Deviation 0.012429	0.02662 One per hour (1/hour) Standard Deviation 0.0047866	0.02204 One per hour (1/hour) Standard Deviation 0.0061504

PRIMARY outcome

Timeframe: 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.

PK: t½ of Selpercatinib.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib in Plasma	24.854 hours (hr) Standard Deviation 4.0850	22.632 hours (hr) Standard Deviation 8.7328	27.139 hours (hr) Standard Deviation 7.1091	33.828 hours (hr) Standard Deviation 10.4879

PRIMARY outcome

Timeframe: 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.

PK: CL/F of Selpercatinib

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
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	7.188 Liters per Hour (L/h) Standard Deviation 2.6117	5.581 Liters per Hour (L/h) Standard Deviation 1.3807	9.184 Liters per Hour (L/h) Standard Deviation 6.5822

PRIMARY outcome

Timeframe: 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.

PK: Vz/F of Selpercatinib

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
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	227.9 Liter Standard Deviation 106.14	219.4 Liter Standard Deviation 82.255	444.7 Liter Standard Deviation 309.92

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Unbound AUC0-t (AUC0-t,u) of Selpercatinib in Plasma	533.1 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 54.3	659.7 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 24.4	856.3 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 28.0	709.9 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 93.0

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Unbound AUC0-inf (AUC0-inf,u) of Selpercatinib in Plasma	535.7 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 54.3	661.6 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 24.4	862.1 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 28.1	722.3 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 93.9

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Unbound Cmax (Cmax,u) of Selpercatinib in Plasma	37.72 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 113.6	63.23 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 23.4	50.95 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 28.5	34.60 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 187.8

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Unbound CL/F (CL/F,u) of Selpercatinib in Plasma	337.9 Liters per Hour (L/h) Standard Deviation 194.45	247.9 Liters per Hour (L/h) Standard Deviation 58.030	191.6 Liters per Hour (L/h) Standard Deviation 49.277	300.6 Liters per Hour (L/h) Standard Deviation 294.31

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Unbound Vz/F (Vz/F,u) of Selpercatinib in Plasma	12700 Liter (L) Standard Deviation 9498.5	8214 Liter (L) Standard Deviation 4487.5	7697 Liter (L) Standard Deviation 3676.1	14340 Liter (L) Standard Deviation 12842

PRIMARY outcome

Timeframe: 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.

PK: CumAe was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Cumulative Amount of Selpercatinib Excreted (CumAe) in Urine	16.14 milligram (mg) Standard Deviation 9.5297	14.54 milligram (mg) Standard Deviation 3.1611	13.94 milligram (mg) Standard Deviation 5.3203	7.652 milligram (mg) Standard Deviation 5.4210

PRIMARY outcome

Timeframe: 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.

PK: Cum%Dose was reported. The urine sampling time points from pre-dose through 168 hours post-dose were used to assess this outcome.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Cumulative Percentage of Administered Selpercatinib Dose (Cum%Dose) Excreted in Urine	10.09 percentage of dose excreted Standard Deviation 5.9560	9.087 percentage of dose excreted Standard Deviation 1.9757	8.713 percentage of dose excreted Standard Deviation 3.3252	4.782 percentage of dose excreted Standard Deviation 3.3881

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selpercatinib (Control; Normal Renal Function) n=10 Participants 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.	Selpercatinib (Mild Renal Impairment) n=8 Participants 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.	Selpercatinib (Moderate Renal Impairment) n=8 Participants 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.	Selpercatinib (Severe Renal Impairment) n=7 Participants 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.
PK: Renal Clearance (CLr) of Selpercatinib in Urine	735.9 milliliter per hour (mL/hr) Standard Deviation 230.39	641.6 milliliter per hour (mL/hr) Standard Deviation 243.96	480.4 milliliter per hour (mL/hr) Standard Deviation 208.23	314.6 milliliter per hour (mL/hr) Standard Deviation 94.084

Adverse Events

Selpercatinib (Control; Normal Renal Function)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Selpercatinib (Mild Renal Impairment)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Selpercatinib (Moderate Renal Impairment)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Selpercatinib (Severe Renal Impairment)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Selpercatinib (Control; Normal Renal Function) n=13 participants at risk 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.	Selpercatinib (Mild Renal Impairment) n=9 participants at risk 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.	Selpercatinib (Moderate Renal Impairment) n=8 participants at risk 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.	Selpercatinib (Severe Renal Impairment) n=7 participants at risk 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.
Gastrointestinal disorders Abdominal distension	0.00% 0/13 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	11.1% 1/9 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/7 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Gastrointestinal disorders Constipation	7.7% 1/13 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	11.1% 1/9 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/7 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Gastrointestinal disorders Diarrhoea	7.7% 1/13 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/9 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	14.3% 1/7 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Gastrointestinal disorders Dry mouth	0.00% 0/13 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	11.1% 1/9 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/7 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Gastrointestinal disorders Nausea	0.00% 0/13 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	22.2% 2/9 • Number of events 2 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/7 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/9 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/7 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/13 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/9 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	14.3% 1/7 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Nervous system disorders Dizziness	0.00% 0/13 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/9 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	14.3% 1/7 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Nervous system disorders Head discomfort	0.00% 0/13 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	11.1% 1/9 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/7 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Nervous system disorders Headache	7.7% 1/13 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/9 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	25.0% 2/8 • Number of events 2 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/7 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Nervous system disorders Somnolence	0.00% 0/13 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	22.2% 2/9 • Number of events 2 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	12.5% 1/8 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/7 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/13 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/9 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	0.00% 0/8 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.	14.3% 1/7 • Number of events 1 • Baseline up to 15 days All enrolled participants who received at least one dose of Selpercatinib.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60