Study of H2 Antagonist and a Proton Pump Inhibitor of Selpercatinib in Healthy Participants

Study Overview
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Brief Summary
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The main purpose of this study is to learn about how H2 antagonist (ranitidine) and proton pump inhibitor (PPI) (omeprazole) affect Selpercatinib in healthy participants. Information about safety and tolerability will be collected. The study will last up to about 9 weeks, inclusive of screening period.

Official Title
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An Open-Label, 3-Period, Fixed Sequence Study to Evaluate the Effect of an H2 Antagonist 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: Ranitidine
* Drug: Omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or 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30 days or any other type of medical research judged to be incompatible with this study Have previously participated or withdrawn from this study Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to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: 160 milligram (mg) Selpercatinib<br>Participants received a single oral dose of 160 mg Selpercatinib. | Drug: Selpercatinib<br>* Administered orally.<br>* Other names: LOXO-292;|
| Experimental: 150 mg Ranitidine and 160 mg Selpercatinib<br>Participants received 150 mg ranitidine twice a day orally for 11 days and a single oral dose of 160 mg Selpercatinib. | Drug: Selpercatinib<br>* Administered orally.<br>* Other names: LOXO-292;Drug: Ranitidine<br>* Administered orally.<br>|
| Experimental: 40 mg Omeprazole and 160 mg Selpercatinib<br>Participants received 40 mg omeprazole once daily for 11 days and a single oral dose of 160 mg Selpercatinib. | 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 (Days 1, 12, and 23) | 
| 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 (Days 1, 12, and 23) | 
| PK: Extrapolation for area under the concentration time curve (%AUCextrap) of Selpercatinib | PK: %AUCextrap of Selpercatinib | Pre-dose up to 168 hour post-dose (Days 1, 12, and 23) | 
| PK: Maximum observed concentration (Cmax) of Selpercatinib | PK: Cmax of Selpercatinib | Pre-dose up to 168 hour post-dose (Days 1, 12, and 23) | 
| PK: Time to reach Cmax (Tmax) of Selpercatinib | PK: Tmax of Selpercatinib | Pre-dose up to 168 hour post-dose (Days 1, 12, and 23) | 
| PK: Elimination rate constant (λZ) of Selpercatinib | PK: λZ of Selpercatinib | Pre-dose up to 168 hour post-dose (Days 1, 12, and 23) | 
| 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 (Days 1, 12, and 23) | 
| PK: Apparent first-order terminal elimination half-life (t½) of Selpercatinib | PK: t½ of Selpercatinib | Pre-dose up to 168 hour post-dose (Days 1, 12, and 23) |