A Study of Effects of Selpercatinib (LY3527723) on Midazolam in Healthy Participants

An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of LOXO-292 on the Single Dose Pharmacokinetics of Midazolam in Healthy Adult Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05338476

Enrollment

Registered

2022-04-21

Start date

2018-07-12

Completion date

2018-09-18

Last updated

2025-10-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

The main purpose of this study is to assess the effect of selpercatinib on how fast midazolam gets into the blood stream and how long it takes the body to remove it when administered in healthy participants. Information about safety and tolerability will be collected. The study will last up to about 6 weeks, inclusive of screening period.

Interventions

DRUGMidazolam

Administered orally.

DRUGSelpercatinib

Administered orally.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

: * Male and female participants of non-childbearing potential who are agreeable to take birth control measures until study completion * Body mass index (BMI) ≥ 18.0 and ≤ 32.0 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

Exclusion criteria

* Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study * Have previously participated or withdrawn from this study * Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study * Had blood loss of more than 500 milliliters (mL) within the previous 30 days of study screening * Require treatment with inducers or inhibitors of cytochrome P450 (CYP) CYP3A within 14 days before the first dose of study drug through the end of Period 2

Design outcomes

Primary

Measure	Time frame	Description
PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Midazolam	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: Vz/F of midazolam was reported.
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: PK: AUC0-inf of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: PK: AUC%extrap of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: Cmax of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: Tmax of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: Kel of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: t½ of midazolam and its metabolite 1-OH-midazolam was reported.
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Midazolam	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: CL/F of midazolam was reported.

Secondary

Measure	Time frame	Description
PK: Area Under the Concentration-time Curve During a Dosing Interval (Tau) at Steady State (AUCtau) of Selpercatinib	Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: AUC0-tau of Selpercatinib was reported.
PK: Maximum Observed Concentration (Cmax) of Selpercatinib	Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)	PK: Cmax of Selpercatinib was reported.
PK: Maximum Observed Concentration at Steady-state (Cmax,ss) of Selpercatinib	Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: Cmax,ss of Selpercatinib was reported.
PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Period 2: Predose at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9	PK: Ctrough of Selpercatinib was reported.
PK: Time to Reach Maximum Observed Concentration (Tmax) of Selpercatinib	Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)	PK: tmax of Selpercatinib was reported.
PK: Time to Reach Maximum Observed Concentration at Steady-state (Tmax,ss) of Selpercatinib	Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: Tmax,ss of Selpercatinib was reported.
PK: Apparent Total Plasma Clearance at Steady State After Oral/Extravascular Administration (CL,ss/F) of Selpercatinib	Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)	PK: CL,ss/F of Selpercatinib was reported.
PK: Area Under the Concentration-time Curve, From Time 0 to the 12 Hour (AUC0-12) of Selpercatinib	Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)	PK: AUC0-12 of Selpercatinib was reported.

Countries

United States

Participant flow

Participants by arm

Arm	Count
All Participants * Period 1: Participants received single oral dose of 2 milligram (mg) midazolam syrup on Day 1. * Period 2: Participants received 160 mg Selpercatinib capsules twice daily (BID) from Day 1-10, and on Day 10 it was co-administered with a single oral dose of 2 mg midazolam syrup on the morning of Day 10.	16
Total	16

Withdrawals & dropouts

Period	Reason	FG000	FG001
Period 2	Adverse Event	0	1

Baseline characteristics

Characteristic	All Participants
Age, Continuous	41.1 years STANDARD_DEVIATION 6.05
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	15 Participants
Region of Enrollment United States	16 Participants
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 16	0 / 15
other Total, other adverse events	5 / 16	12 / 16	4 / 15
serious Total, serious adverse events	0 / 16	0 / 16	0 / 15

Outcome results

Primary

Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)

PK: PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam was reported.

Time frame: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)	Midazolam	27.02 nanogramhour per milliliter (ngh/mL)	Geometric Coefficient of Variation 38.4
Period 1: Midazolam	Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)	Metabolite: 1-OH-midazolam	41.02 nanogramhour per milliliter (ngh/mL)	Geometric Coefficient of Variation 100.7
Period 2: Selpercatinib+ Midazolam	Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)	Midazolam	42.43 nanogramhour per milliliter (ngh/mL)	Geometric Coefficient of Variation 35.5
Period 2: Selpercatinib+ Midazolam	Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)	Metabolite: 1-OH-midazolam	55.81 nanogramhour per milliliter (ngh/mL)	Geometric Coefficient of Variation 80.5

Primary

PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam

PK: t½ of midazolam and its metabolite 1-OH-midazolam was reported.

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	5.812 hours	Geometric Coefficient of Variation 32.5
Period 1: Midazolam	PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	6.275 hours	Geometric Coefficient of Variation 31.4
Period 2: Selpercatinib+ Midazolam	PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	7.082 hours	Geometric Coefficient of Variation 22.1
Period 2: Selpercatinib+ Midazolam	PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	7.317 hours	Geometric Coefficient of Variation 18.2

Primary

PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Kel of midazolam and its metabolite 1-OH-midazolam was reported.

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	0.1193 One per hour (1/h)	Geometric Coefficient of Variation 32.5
Period 1: Midazolam	PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	0.1105 One per hour (1/h)	Geometric Coefficient of Variation 31.4
Period 2: Selpercatinib+ Midazolam	PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	0.09787 One per hour (1/h)	Geometric Coefficient of Variation 22.1
Period 2: Selpercatinib+ Midazolam	PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	0.09474 One per hour (1/h)	Geometric Coefficient of Variation 18.2

Primary

PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Midazolam

PK: CL/F of midazolam was reported.

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Midazolam	70.26 Liter per Hour (L/h)	Geometric Coefficient of Variation 38.4
Period 2: Selpercatinib+ Midazolam	PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Midazolam	44.44 Liter per Hour (L/h)	Geometric Coefficient of Variation 36.7

Primary

PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Midazolam

PK: Vz/F of midazolam was reported.

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Midazolam	589.1 Liter (L)	Geometric Coefficient of Variation 35
Period 2: Selpercatinib+ Midazolam	PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Midazolam	454.1 Liter (L)	Geometric Coefficient of Variation 32.3

Primary

PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam

PK: PK: AUC0-inf of midazolam and its metabolite 1-OH-midazolam was reported.

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	28.46 nanogramhour per milliliter (ngh/mL)	Geometric Coefficient of Variation 38.4
Period 1: Midazolam	PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	43.29 nanogramhour per milliliter (ngh/mL)	Geometric Coefficient of Variation 100.3
Period 2: Selpercatinib+ Midazolam	PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	45.00 nanogramhour per milliliter (ngh/mL)	Geometric Coefficient of Variation 36.7
Period 2: Selpercatinib+ Midazolam	PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	59.49 nanogramhour per milliliter (ngh/mL)	Geometric Coefficient of Variation 80.2

Primary

PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Cmax of midazolam and its metabolite 1-OH-midazolam was reported.

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	11.94 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 32
Period 1: Midazolam	PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	15.98 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 70.1
Period 2: Selpercatinib+ Midazolam	PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	16.76 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 39.9
Period 2: Selpercatinib+ Midazolam	PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	17.91 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 70.3

Primary

PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam

PK: PK: AUC%extrap of midazolam and its metabolite 1-OH-midazolam was reported.

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	4.763 percent AUC extrapolation	Geometric Coefficient of Variation 36.9
Period 1: Midazolam	PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	4.869 percent AUC extrapolation	Geometric Coefficient of Variation 41.3
Period 2: Selpercatinib+ Midazolam	PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	5.165 percent AUC extrapolation	Geometric Coefficient of Variation 48.1
Period 2: Selpercatinib+ Midazolam	PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	5.849 percent AUC extrapolation	Geometric Coefficient of Variation 36.3

Primary

PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Tmax of midazolam and its metabolite 1-OH-midazolam was reported.

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	0.584 hours	Geometric Coefficient of Variation 20.4
Period 1: Midazolam	PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	0.668 hours	Geometric Coefficient of Variation 25.3
Period 2: Selpercatinib+ Midazolam	PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam	Midazolam	0.626 hours	Geometric Coefficient of Variation 33.6
Period 2: Selpercatinib+ Midazolam	PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam	Metabolite: 1-OH-midazolam	0.738 hours	Geometric Coefficient of Variation 30.6

Secondary

PK: Apparent Total Plasma Clearance at Steady State After Oral/Extravascular Administration (CL,ss/F) of Selpercatinib

PK: CL,ss/F of Selpercatinib was reported.

Time frame: Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome. 'Number analyzed' signifies participants with available data at specified timepoints.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Apparent Total Plasma Clearance at Steady State After Oral/Extravascular Administration (CL,ss/F) of Selpercatinib	Day 9	1.930 Liter per Hours (L/h)	Geometric Coefficient of Variation 35.8
Period 1: Midazolam	PK: Apparent Total Plasma Clearance at Steady State After Oral/Extravascular Administration (CL,ss/F) of Selpercatinib	Day 10	2.027 Liter per Hours (L/h)	Geometric Coefficient of Variation 34.5

Secondary

PK: Area Under the Concentration-time Curve During a Dosing Interval (Tau) at Steady State (AUCtau) of Selpercatinib

PK: AUC0-tau of Selpercatinib was reported.

Time frame: Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Area Under the Concentration-time Curve During a Dosing Interval (Tau) at Steady State (AUCtau) of Selpercatinib	Day 9	37610 ng*h/mL	Geometric Coefficient of Variation 32.4
Period 1: Midazolam	PK: Area Under the Concentration-time Curve During a Dosing Interval (Tau) at Steady State (AUCtau) of Selpercatinib	Day 10	36890 ng*h/mL	Geometric Coefficient of Variation 33.5

Secondary

PK: Area Under the Concentration-time Curve, From Time 0 to the 12 Hour (AUC0-12) of Selpercatinib

PK: AUC0-12 of Selpercatinib was reported.

Time frame: Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Area Under the Concentration-time Curve, From Time 0 to the 12 Hour (AUC0-12) of Selpercatinib	10710 ng*h/mL	Geometric Coefficient of Variation 36.9

Secondary

PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib

PK: Ctrough of Selpercatinib was reported.

Time frame: Period 2: Predose at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 1	1301 ng/mL	Geometric Coefficient of Variation 23.1
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 2	1843 ng/mL	Geometric Coefficient of Variation 27.6
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 3	2022 ng/mL	Geometric Coefficient of Variation 29.4
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 4	2213 ng/mL	Geometric Coefficient of Variation 35.5
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 5	2373 ng/mL	Geometric Coefficient of Variation 34.9
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 6	2660 ng/mL	Geometric Coefficient of Variation 37.6
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 7	2606 ng/mL	Geometric Coefficient of Variation 32.7
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 8	2733 ng/mL	Geometric Coefficient of Variation 26
Period 1: Midazolam	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	Day 9	2754 ng/mL	Geometric Coefficient of Variation 30.9

Secondary

PK: Maximum Observed Concentration at Steady-state (Cmax,ss) of Selpercatinib

PK: Cmax,ss of Selpercatinib was reported.

Time frame: Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Maximum Observed Concentration at Steady-state (Cmax,ss) of Selpercatinib	Day 9	4574 ng/mL	Geometric Coefficient of Variation 38
Period 1: Midazolam	PK: Maximum Observed Concentration at Steady-state (Cmax,ss) of Selpercatinib	Day 10	4190 ng/mL	Geometric Coefficient of Variation 36.8

Secondary

PK: Maximum Observed Concentration (Cmax) of Selpercatinib

PK: Cmax of Selpercatinib was reported.

Time frame: Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Maximum Observed Concentration (Cmax) of Selpercatinib	1859 ng/mL	Geometric Coefficient of Variation 50.3

Secondary

PK: Time to Reach Maximum Observed Concentration at Steady-state (Tmax,ss) of Selpercatinib

PK: Tmax,ss of Selpercatinib was reported.

Time frame: Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile for this outcome.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Time to Reach Maximum Observed Concentration at Steady-state (Tmax,ss) of Selpercatinib	Day 9	1.955 hours	Geometric Coefficient of Variation 76
Period 1: Midazolam	PK: Time to Reach Maximum Observed Concentration at Steady-state (Tmax,ss) of Selpercatinib	Day 10	1.752 hours	Geometric Coefficient of Variation 55.8

Secondary

PK: Time to Reach Maximum Observed Concentration (Tmax) of Selpercatinib

PK: tmax of Selpercatinib was reported.

Time frame: Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)

Population: All participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Period 1: Midazolam	PK: Time to Reach Maximum Observed Concentration (Tmax) of Selpercatinib	1.843 hours	Geometric Coefficient of Variation 45.9

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

A Study of Effects of Selpercatinib (LY3527723) on Midazolam in Healthy Participants

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)

PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Midazolam

PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Midazolam

PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam

PK: Apparent Total Plasma Clearance at Steady State After Oral/Extravascular Administration (CL,ss/F) of Selpercatinib

PK: Area Under the Concentration-time Curve During a Dosing Interval (Tau) at Steady State (AUCtau) of Selpercatinib

PK: Area Under the Concentration-time Curve, From Time 0 to the 12 Hour (AUC0-12) of Selpercatinib

PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib

PK: Maximum Observed Concentration at Steady-state (Cmax,ss) of Selpercatinib

PK: Maximum Observed Concentration (Cmax) of Selpercatinib

PK: Time to Reach Maximum Observed Concentration at Steady-state (Tmax,ss) of Selpercatinib

PK: Time to Reach Maximum Observed Concentration (Tmax) of Selpercatinib