A Study of the Effects of Pirtobrutinib (LOXO-305) on Repaglinide (CYP2C8 Substrate) in Healthy Participants

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the effect of pirtobrutinib (LOXO-305) on single oral dose of repaglinide (CYP2C8 substrate) when administered as multiple doses by conducting the blood tests to measure how much pirtobrutinib (LOXO-305) is in the bloodstream and how the body handles and eliminates pirtobrutinib (LOXO-305) in adult healthy participants. The study will also evaluate the safety and tolerability of pirtobrutinib (LOXO-305). The study is conducted in two periods. Participants will stay in this study for up to 54 days.

Official Title
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A Phase I, Open-label, Fixed-sequence, Drug Interaction Study to Investigate the Effect of Multiple Oral Doses of Pirtobrutinib (LOXO-305) on the Pharmacokinetics of Repaglinide (CYP2C8 Substrate) in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Repaglinide
* Drug: Pirtobrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator Female participants of non-childbearing potential and male participants who follow standard contraceptive methods Must have comply with all study procedures, including the 16-night stay at the Clinical Research Unit (CRU) and follow-up phone call Exclusion Criteria: History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor Known ongoing alcohol and/or drug abuse within 2 years prior to Screening History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (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: Pirtobrutinib - Period 2<br>Multiple doses of pirtobrutinib administered orally. | Drug: Pirtobrutinib<br>* Administered orally.<br>* Other names: LY3527727;|
| Experimental: Pirtobrutinib + Repaglinide - Period 2<br>Pirtobrutinib administered in combination with repaglinide orally. There will be a washout period of 11 days between the dose of repaglinide from Period 1 to 2. | Drug: Repaglinide<br>* Administered orally.<br>Drug: Pirtobrutinib<br>* Administered orally.<br>* Other names: LY3527727;|

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 Measurable Concentration (AUC0-t) of Repaglinide | PK: AUC0-t of Repaglinide | Pre-dose up to 24 hours post-dose on Day 1 | 
| 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 24 hours post-dose on Day 1 | 
| PK: Percentage of AUC0-inf extrapolated (AUC%extrap) of Repaglinide | PK: AUC%extrap of Repaglinide | Pre-dose up to 24 hours post-dose on Day 1 | 
| PK: Maximum observed concentration (Cmax) of Repaglinide | PK: Cmax of Repaglinide | Pre-dose up to 24 hours post-dose on Day 1 | 
| PK: Time to reach Cmax (Tmax) of Repaglinide | PK: Tmax of Repaglinide | Pre-dose up to 24 hours post-dose on Day 1 | 
| PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | PK: Lambda Z of Repaglinide | Pre-dose up to 24 hours post-dose on Day 1 | 
| PK: Apparent Systemic Clearance (CL/F) of Repaglinide | PK: CL/F of Repaglinide | Pre-dose up to 24 hours post-dose on Day 1 | 
| PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide | PK: t½ of Repaglinide | Pre-dose up to 24 hours post-dose on Day 1 | 
| PK: Apparent Volume of Distribution (Vz/F) of Repaglinide | PK: Vz/F of Repaglinide | Pre-dose up to 24 hours post-dose on Day 1 | 
| PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | PK: AUC0-t of Pirtobrutinib | Pre-dose on Days 2 to 11 | 
| PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib | PK: AUCtau of Pirtobrutinib | Pre-dose on Days 2 to 11 | 
| PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib | PK: Cmax of Pirtobrutinib | Pre-dose on Days 2 to 11 | 
| PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib | PK: Ctrough of Pirtobrutinib | Pre-dose on Days 2 to 11 | 
| PK: Time to reach Cmax (Tmax) of Pirtobrutinib | PK: Tmax of Pirtobrutinib | Pre-dose on Days 2 to 11 | 
| PK: Apparent Systemic Clearance (CL/F) at steady state (CL,ss/F) of Pirtobrutinib | PK: CL,ss/F of Pirtobrutinib | Pre-dose on Days 2 to 11 |