A Study of Effect of Food and a Proton Pump Inhibitor on Selpercatinib (LY3527723) 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 food on how fast selpercatinib gets into the bloodstream and how long it takes the body to remove it after a high-fat meal, and the effect of a change in gastric pH after multiple doses of omeprazole on how fast selpercatinib gets into the bloodstream and how long it takes the body to remove it when administered under fasted and fed conditions in healthy participants. The study will also evaluate the safety and tolerability of selpercatinib in healthy participants. The study will last up to 33 days excluding the screening period.

Official Title
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An Open-Label, Randomized, Crossover Study to Evaluate the Effect of Food and a Proton Pump Inhibitor on the Single-Dose Pharmacokinetics of LOXO-292 in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Selpercatinib
* Drug: Omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-vasectomized, male participants must have agreed to use a condom with spermicide or abstain from sexual intercourse during the study until 6 months after the last dosing. (No restrictions were required for a vasectomized male provided his vasectomy had been performed 4 months or more prior to the first dosing of study drug) If male, must have agreed not to donate sperm from the first dosing until 6 months after the last dosing 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: Had a history of gastritis, gastrointestinal tract or hepatic disorder or other clinical condition that might have, in the opinion of the Principal Investigator or designee, and as confirmed by the Sponsor, affected the absorption, distribution, biotransformation, or excretion of LOXO 292 or omeprazole

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selpercatinib and omeprazole administered in ABCD treatment sequence<br>Period 1: Single oral dose of Selpercatinib administered in fasted state. Period 2: Single oral dose of Selpercatinib administered in fed state. Period 3: Multiple daily oral doses of omeprazole administered along with single oral dose of selpercatinib in fasted state. Period 4: Multiple daily oral doses of omeprazole administered along with single oral dose of selpercatinib in fed state. Periods 1 and 2, 2 and 3 will be separated by a 7-day washout period. There will be no washout between Periods 3 and 4. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;Drug: Omeprazole<br>* Administered orally<br>|
| Experimental: Selpercatinib and omeprazole administered in ABDC treatment sequence.<br>Period 1: Single oral dose of Selpercatinib administered in fasted state. Period 2: Single oral dose of Selpercatinib administered in fed state. Period 3: Multiple daily oral doses of omeprazole administered along with single oral dose of selpercatinib in fed state. Period 4: Multiple daily oral doses of omeprazole administered along with single oral dose of selpercatinib in fasted state. Periods 1 and 2, 2 and 3 will be separated by a 7-day washout period. There will be no washout between Periods 3 and 4. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;Drug: Omeprazole<br>* Administered orally<br>|
| Experimental: Selpercatinib and omeprazole administered in BACD treatment sequence.<br>Period 1: Single oral dose of Selpercatinib administered in fed state. Period 2: Single oral dose of Selpercatinib administered in fasted state. Period 3: Multiple daily oral doses of omeprazole administered along with single oral dose of selpercatinib in fasted state. Period 4: Multiple daily oral doses of omeprazole administered along with single oral dose of selpercatinib in fed state. Periods 1 and 2, 2 and 3 will be separated by a 7-day washout period. There will be no washout between Periods 3 and 4. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;Drug: Omeprazole<br>* Administered orally<br>|
| Experimental: Selpercatinib and omeprazole administered in BADC treatment sequence.<br>Period 1: Single oral dose of Selpercatinib administered in fed state. Period 2: Single oral dose of Selpercatinib administered in fasted state. Period 3: Multiple daily oral doses of omeprazole administered along with single oral dose of selpercatinib in fed state. Period 4: Multiple daily oral doses of omeprazole administered along with single oral dose of selpercatinib in fasted state. Periods 1 and 2, 2 and 3 will be separated by a 7-day washout period. There will be no washout between Periods 3 and 4. | Drug: Selpercatinib<br>* Administered orally<br>* Other names: LOXO-292;Drug: Omeprazole<br>* Administered orally<br>|

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 Selpercatinib | PK: AUC0-t of Selpercatinib | Pre-dose up to 168 hour post-dose | 
| PK: Area under the concentration-time curve, from time 0 extrapolated to infinity (AUC0-inf) of Selpercatinib | PK: AUC0-inf of Selpercatinib | Pre-dose up to 168 hour post-dose | 
| PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Selpercatinib | PK: AUC%extrap of Selpercatinib | Pre-dose up to 168 hour post-dose | 
| PK: Maximum observed concentration (Cmax) of Selpercatinib | PK: Cmax of Selpercatinib | Pre-dose up to 168 hour post-dose | 
| PK: Time to reach Cmax (Tmax) of Selpercatinib | PK: Tmax of Selpercatinib | Pre-dose up to 168 hour post-dose | 
| PK: Apparent first order terminal elimination rate constant (Kel) of Selpercatinib | PK: Kel of Selpercatinib | Pre-dose up to 168 hour post-dose | 
| PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Selpercatinib | PK: CL/F of Selpercatinib | Pre-dose up to 168 hour post-dose | 
| PK: Apparent first-order terminal elimination half-life (t½) of Selpercatinib | PK: t½ of Selpercatinib | Pre-dose up to 168 hour post-dose |