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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06165146
• Other study ID #: LOXO-BTK-20016
• Secondary ID: J2N-OX-JZNL
• Status: Completed
• Phase: Phase 1
• Start date: November 10, 2020
• Est. completion date: December 30, 2020

Study information

• Verified date: November 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 30, 2020
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Repaglinide
Administered orally.
• Pirtobrutinib
Administered orally.

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit	Daytona Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	PK: Maximum observed concentration (Cmax) of Repaglinide	PK: Cmax of Repaglinide	Pre-dose up to 24 hours post-dose on Day 1
Primary	PK: Time to reach Cmax (Tmax) of Repaglinide	PK: Tmax of Repaglinide	Pre-dose up to 24 hours post-dose on Day 1
Primary	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
Primary	PK: Apparent Systemic Clearance (CL/F) of Repaglinide	PK: CL/F of Repaglinide	Pre-dose up to 24 hours post-dose on Day 1
Primary	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
Primary	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
Primary	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
Primary	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
Primary	PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib	PK: Cmax of Pirtobrutinib	Pre-dose on Days 2 to 11
Primary	PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib	PK: Ctrough of Pirtobrutinib	Pre-dose on Days 2 to 11
Primary	PK: Time to reach Cmax (Tmax) of Pirtobrutinib	PK: Tmax of Pirtobrutinib	Pre-dose on Days 2 to 11
Primary	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