A Study of Effects of Selpercatinib (LY3527723) on Repaglinide 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 repaglinide 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 12 days.

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 Repaglinide in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Repaglinide
* Drug: Selpercatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Hemoglobin (Hb) A1c value < 6.5 % at screening and fasting glucose ≤ 126 mg/dL. Males who are capable of fathering a child must agree to use one of the following methods of contraception from the time of the dose administration through 6 months after the last dose Female of non-childbearing potential only or must have undergone sterilization procedures at least 6months prior to the first dosing Exclusion Criteria: History or presence of diabetes or history of prior episode(s) of hypoglycemia. Estimated creatinine clearance <90 mL/min at Screening or Check-in (Day -1, Period 1) Unable to refrain from or anticipates the use of any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements for 14 days prior to the first dosing and through EOT or ET. After first dosing, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the PI or designee

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: Repaglinide - Period 1<br>Single dose of repaglinide administered orally. | Drug: Repaglinide<br>* Administered orally.<br>|
| Experimental: Selpercatinib and repaglinide - Period 2<br>Multiple doses of selpercatinib along with single dose of repaglinide administered orally. There will be a 24-hour washout period between Period 1 and 2. | Drug: Repaglinide<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 Repaglinide | PK: AUC0-t of Repaglinide | Pre-dose up to 16 hours postdose | 
| PK: Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of Repaglinide | PK: AUC0-inf of Repaglinide | Pre-dose up to 16 hours post-dose | 
| PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Repaglinide | PK: AUC%extrap of Repaglinide | Pre-dose up to 16 hours post-dose | 
| PK: Maximum observed concentration (Cmax) of Repaglinide | PK: Cmax of Repaglinide | Pre-dose up to 16 hours post-dose | 
| PK: Time to reach Cmax (Tmax) of Repaglinide | PK: Tmax of Repaglinide | Pre-dose up to 16 hour post-dose | 
| PK: Apparent first-order terminal elimination rate constant (Kel) of Repaglindide | PK: Kel of Repaglindide | Pre-dose up to 16 hour post-dose | 
| PK: Apparent first-order terminal elimination half-life (t½) of Repaglinide | PK: t½ of Repaglinide | Pre-dose up to 16 hour post-dose | 
| PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Repaglinide | PK: CL/F of Repaglinide | Pre-dose up to 16 hour post-dose | 
| PK: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F) of Repaglinide | PK: (Vz/F) of Repaglinide | Pre-dose up to 16 hour post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK: Area under the concentration-time curve, from time 0 to the 12 hour timepoint (AUC0-12) of Selpercatinib (Day 1 of Period 2) | PK: AUC0-12 of Selpercatinib | Pre-morning dose up to 12 hours following the morning dose | 
| PK: Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Selpercatinib (Day 1 of Period 2) | PK: AUC0-t of Selpercatinib | Pre-morning dose up to 12 hours following the morning dose | 
| PK: Maximum observed concentration (Cmax) of Selpercatinib (Day 1 of Period 2) | PK: Cmax of Selpercatinib | Pre-morning dose up to 12 hours following the morning dose | 
| PK: Time to reach Cmax (Tmax) of Selpercatinib (Day 1 of Period 2) | PK: Tmax of Selpercatinib | Pre-morning dose up to 12 hours following the morning dose | 
| PK: Area under the concentration-time curve during a dosing interval (tau) at steady state (AUCtau) of Selpercatinib (Day 10 of Period 2) | PK: AUCtau of Selpercatinib | Pre-morning dose up to 12 hours following the morning dose | 
| PK: Maximum observed concentration at steady-state (Cmax,ss) of Selpertcatinib (Day 10 of Period 2) | PK: Cmax,ss of Selpertcatinib | Pre-morning dose up to 12 hours following the morning dose | 
| PK: Concentration observed at the end of the dosing interval (Ctrough) of Selpercatinib (Day 10 of Period 2) | PK: Ctrough of Selpercatinib | Pre-morning dose | 
| PK: Time to reach Cmax,ss (Tmax,ss) of Selpercatinib (Day 10 of Period 2) | PK: Tmax,ss of Selpercatinib | Pre-morning dose up to 12 hours following the morning dose | 
| PK: Apparent total plasma clearance after oral (extravascular) administration(CL,ss/F) of Selpercatinib (Day 10 of Period 2) | PK: CL,ss/F of Selpercatinib | Pre-morning dose up to 12 hours following the morning dose |