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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Midazolam
* Drug: Selpercatinib


Participation Criteria
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Eligibility Criteria
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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30 days or any other type of medical research judged to be incompatible with this study Have previously participated or withdrawn from this study Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam<br>Midazolam administered orally. | Drug: Midazolam<br>* Administered orally.<br>|
| Experimental: Selpercatinib and Midazolam<br>Selpercatinib and midazolam administered orally. | Drug: Midazolam<br>* Administered orally.<br>Drug: Selpercatinib<br>* Administered orally.<br>* Other names: LOXO-292;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Midazolam | PK: AUC0-t of Midazolam | Days 1, 2, 10, and 11 | 
| PK: Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of Midazolam | PK: AUC0-inf of Midazolam | Days 1, 2, 10, and 11 | 
| PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Midazolam | PK: AUC%extrap of Midazolam | Days 1, 2, 10, and 11 | 
| PK: Maximum observed concentration (Cmax) of Midazolam | PK: Cmax of Midazolam | Days 1, 2, 10, and 11 | 
| PK: Time to reach Cmax (Tmax) of Midazolam | PK: Tmax of Midazolam | Days 1, 2, 10, and 11 | 
| PK: Apparent first-order terminal elimination rate constant (Kel) of Midazolam | PK: Kel of Midazolam | Days 1, 2, 10, and 11 | 
| PK: Apparent first-order terminal elimination half-life (t½) of Midazolam | PK: t½ of Midazolam | Days 1, 2, 10, and 11 | 
| PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Midazolam | PK: CL/F of Midazolam | Days 1, 2, 10, and 11 | 
| PK: Apparent volume of distribution during the terminal elimination phase (Vz/F) of Midazolam | PK: Vz/F of Midazolam | Days 1, 2, 10, and 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK : Area under the concentration-time curve, from time 0 to the 12 hour (AUC0-12) of Selpercatinib | PK: AUC0-12 of Selpercatinib | Day 1 | 
| PK: Area under the concentration-time curve during a dosing interval (tau) at steady state (AUCtau) of Selpercatinib | AUCtau of Selpercatinib | Days 1-11 | 
| PK: Cmax of Selpercatinib | PK: Cmax of Selpercatinib | Days 1-11 | 
| PK: Maximum observed concentration at steady-state (Cmax,ss) of Selpercatinib | PK: Cmax,ss of Selpercatinib | Days 1-11 | 
| PK: Concentration observed at the end of the dosing interval (Ctrough) of Selpercatinib | PK: Ctrough of Selpercatinib | Days 1-11 | 
| PK: Tmax of Selpercatinib | PK: Tmax of Selpercatinib | Days 1-11 | 
| PK: Time to reach Cmax,ss (Tmax,ss) of Selpercatinib | PK: Tmax,ss of Selpercatinib | Days 1-11 | 
| PK: Apparent total plasma clearance (CL,ss/F) of Selpercatinib | PK: CL,ss/F of Selpercatinib | Days 1-11 |