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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Repaglinide; Drug: Pirtobrutinib

• Registration Number: NCT06165146
• Lead Sponsor: Eli Lilly and Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-11-10
• Primary Completion: 2020-12-30
• Study Completion: 2020-12-30
• Study First Submitted: 2023-11-30
• Study First Submitted QC: 2023-12-08
• Study First Posted: 2023-12-11
• Results First Submitted: 2025-01-31
• Status Verified: 2025-03
• Results First Submitted QC: 2025-03-07
• Last Update Submitted: 2025-03-07
• Results First Posted: 2025-03-17
• Last Update Posted: 2025-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Period 1: 0.5 mg Repaglinide	Repaglinide	Participants received a single oral dose of 0.5 milligrams (mg) repaglinide tablet, in the morning on Day 1.
Period 2: 200 mg Pirtobrutinib QD	Pirtobrutinib	Participants received oral doses of 200 mg pirtobrutinib tablets, once daily (QD) in the morning from Day 2 to Day 11.
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	Repaglinide	Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	Pirtobrutinib	Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: AUC(0-t) of repaglinide was reported.
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: AUC(0-inf) of repaglinide was reported.
PK: Maximum Observed Concentration (Cmax) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: Cmax of repaglinide was reported.
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: AUC-inf (%extrap) of repaglinide was reported.
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: Tmax of repaglinide was reported.
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: Lambda Z of repaglinide was reported.
PK: Apparent Systemic Clearance (CL/F) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: CL/F of repaglinide was reported.
PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: t½ of repaglinide was reported.
PK: Apparent Volume of Distribution (Vz/F) of Repaglinide	Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)	PK: Vz/F of repaglinide was reported.
PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib	Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)	PK: AUC0-t of pirtobrutinib was reported.
PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib	Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)	PK: AUCtau of pirtobrutinib was reported.
PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib	Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)	PK: Cmax of pirtobrutinib was reported.
PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib	Period 2: 24-hour post-dose on Day 12	PK: Ctrough of pirtobrutinib was reported.
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib	Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)	PK: Tmax of pirtobrutinib was reported.
PK: Apparent Systemic Clearance (CL/F) at Steady State of Pirtobrutinib	Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)	PK: CL/F at steady state of pirtobrutinib was reported.

Trial Locations

Locations (1)

Covance Clinical Research Unit; 🇺🇸 Daytona Beach, Florida, United States