NCT06194214

Brief Summary

The main purpose of this study is to evaluate the effect of Pirtobrutinib (LOXO-305) on multiple oral doses of digoxin (P-gp substrate) when administered as single and multiple doses by collecting the blood samples and conducting the blood tests to measure how much digoxin is in the bloodstream and how the body handles and eliminates it in healthy participants. The study will also evaluate the safety and tolerability of Pirtobrutinib. Participants will stay in this study for up to 58 days, including screening.

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 Mar 2021

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

March 11, 2021

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 9, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 9, 2021

Completed
2.5 years until next milestone

First Submitted

Initial submission to the registry

December 13, 2023

Completed
26 days until next milestone

First Posted

Study publicly available on registry

January 8, 2024

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

February 21, 2025

Completed
Last Updated

February 21, 2025

Status Verified

January 1, 2025

Enrollment Period

3 months

First QC Date

December 13, 2023

Results QC Date

January 31, 2025

Last Update Submit

January 31, 2025

Conditions

Healthy

Outcome Measures

Primary Outcomes (15)

  • Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma

    PK: AUC\[0-t\] of Digoxin was reported.

    Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma

    PK: AUC \[tau\] of Digoxin was reported.

    Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma

    PK: CL/F of Digoxin in plasma was reported.

    Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma

    PK: Cmax of Digoxin was reported.

    Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma

    PK: Tmax of Digoxin was reported.

    Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Mean Residence Time (MRT) of Digoxin in Plasma

    PK: MRT of Digoxin was reported.

    Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Cumulative Amount of Drug Excreted Unchanged in Urine (Ae) of Digoxin

    PK: Ae of Digoxin in urine was reported. The urine sampling time points from pre-dose through 24 hours post-dose were used to assess this outcome.

    Day 7 and Day 16: Predose, 6, 12, 24 hours post dose

  • PK: Fraction of Digoxin Excreted Unchanged in Urine (Fe) Expressed as Percentage of Dose Excreted

    PK: Fe of Digoxin was reported. The urine sampling time points from pre-dose through 24 hours post-dose were used to assess this outcome.

    Day 7 and Day 16: Predose, 6, 12, 24 hours post dose

  • PK: Renal Clearance (CLr) of Digoxin in Plasma

    PK: CLr of Digoxin in plasma was reported.

    Day 7: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib in Plasma

    PK: AUC\[0-t\] of Pirtobrutinib was reported.

    Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Area Under the Concentration During a Dosing Interval (AUCtau) of Pirtobrutinib in Plasma

    PK: AUCtau of Pirtobrutinib was reported.

    Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib in Plasma

    PK: CL/F of Pirtobrutinib in plasma was reported.

    Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib in Plasma

    PK: Cmax of Pirtobrutinib was reported.

    Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

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

    PK: Tmax of Pirtobrutinib was reported.

    Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

  • PK: Mean Residence Time (MRT) of Pirtobrutinib in Plasma

    PK: MRT of Pirtobrutinib was reported.

    Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

Study Arms (1)

Digoxin + Pirtobrutinib

EXPERIMENTAL

Participants received oral dose of * 0.25 mg digoxin twice daily (BID) on Day 1 * 0.25 mg digoxin once daily (QD) from Day 2 to Day 7 * 200 mg Pirtobrutinib in combination with 0.25 mg digoxin QD starting from Day 8 to Day 16

Drug: PirtobrutinibDrug: Digoxin

Interventions

PirtobrutinibDRUG

Administered Orally.

Also known as: LOXO-305, LY3527727
Digoxin + Pirtobrutinib
DigoxinDRUG

Administered Orally.

Digoxin + Pirtobrutinib

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 20-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
  • Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus immunoglobulin M (HBV IgM) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening
  • Positive polymerase chain reaction (PCR) test for COVID-19 at Screening or Check-in (Day -1)
  • 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)
  • Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Covance Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

pirtobrutinibDigoxin

Intervention Hierarchy (Ancestors)

Digitalis GlycosidesCardenolidesCardiac GlycosidesCardanolidesSteroidsFused-Ring CompoundsPolycyclic CompoundsGlycosidesCarbohydrates

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company
ClinicalTrials.gov@lilly.com
800-545-5979

Study Officials

  • Renee Ward, MD, PhD

    Loxo Oncology, Inc.

    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

December 13, 2023

First Posted

January 8, 2024

Study Start

March 11, 2021

Primary Completion

June 9, 2021

Study Completion

June 9, 2021

Last Updated

February 21, 2025

Results First Posted

February 21, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)