NCT06165146

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1 healthy

Timeline
Completed

Started Nov 2020

Shorter than P25 for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 10, 2020

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2020

Completed
2.9 years until next milestone

First Submitted

Initial submission to the registry

November 30, 2023

Completed
11 days until next milestone

First Posted

Study publicly available on registry

December 11, 2023

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

March 17, 2025

Completed
Last Updated

March 17, 2025

Status Verified

March 1, 2025

Enrollment Period

2 months

First QC Date

November 30, 2023

Results QC Date

January 31, 2025

Last Update Submit

March 7, 2025

Conditions

Healthy

Outcome Measures

Primary Outcomes (15)

  • Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide

    PK: AUC(0-t) of repaglinide was reported.

    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: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide

    PK: AUC(0-inf) of repaglinide was reported.

    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: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide

    PK: AUC-inf (%extrap) of repaglinide was reported.

    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: Maximum Observed Concentration (Cmax) of Repaglinide

    PK: Cmax of repaglinide was reported.

    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: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide

    PK: Tmax of repaglinide was reported.

    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: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide

    PK: Lambda Z of repaglinide was reported.

    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: Apparent Systemic Clearance (CL/F) of Repaglinide

    PK: CL/F of repaglinide was reported.

    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: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide

    PK: t½ of repaglinide was reported.

    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: Apparent Volume of Distribution (Vz/F) of Repaglinide

    PK: Vz/F of repaglinide was reported.

    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: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib

    PK: AUC0-t of pirtobrutinib was reported.

    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: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib

    PK: AUCtau of pirtobrutinib was reported.

    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: Maximum Observed Concentration (Cmax) of Pirtobrutinib

    PK: Cmax of pirtobrutinib was reported.

    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: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib

    PK: Ctrough of pirtobrutinib was reported.

    Period 2: 24-hour post-dose on Day 12

  • PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib

    PK: Tmax of pirtobrutinib was reported.

    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: Apparent Systemic Clearance (CL/F) at Steady State of Pirtobrutinib

    PK: CL/F at steady state of pirtobrutinib was reported.

    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)

Study Arms (3)

Period 1: 0.5 mg Repaglinide

EXPERIMENTAL

Participants received a single oral dose of 0.5 milligrams (mg) repaglinide tablet, in the morning on Day 1.

Drug: Repaglinide

Period 2: 200 mg Pirtobrutinib QD

EXPERIMENTAL

Participants received oral doses of 200 mg pirtobrutinib tablets, once daily (QD) in the morning from Day 2 to Day 11.

Drug: Pirtobrutinib

Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide

EXPERIMENTAL

Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.

Drug: RepaglinideDrug: Pirtobrutinib

Interventions

RepaglinideDRUG

Administered orally.

Period 1: 0.5 mg RepaglinidePeriod 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
PirtobrutinibDRUG

Administered orally.

Also known as: LOXO-305, LY3527727
Period 2: 200 mg Pirtobrutinib QDPeriod 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Covance Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

MeSH Terms

Interventions

repaglinidepirtobrutinib

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company
ClinicalTrials.gov@lilly.com
08005455979

Study Officials

  • Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

    Eli Lilly and Company

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 30, 2023

First Posted

December 11, 2023

Study Start

November 10, 2020

Primary Completion

December 30, 2020

Study Completion

December 30, 2020

Last Updated

March 17, 2025

Results First Posted

March 17, 2025

Record last verified: 2025-03

Data Sharing

IPD Sharing
Will not share

Locations

US(1)