Skip to main content
OpenTrials
Completed

NCT Number: NCT06194214

A Drug Drug Interaction (DDI) Study of Pirtobrutinib (LOXO-305) and Digoxin (P-Glycoprotein Substrate) in Healthy Participants

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Covance Clinical Research Unit

Madison, Wisconsin, 53704, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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 20-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
  • 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

Treatment and study plan

Pirtobrutinib

Drug

Administered Orally.

Other names: LOXO-305, LY3527727

Digoxin

Drug

Administered Orally.

Primary outcomes

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

    Time frame: 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: AUC[0-t] of Digoxin was reported.

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

    Time frame: 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: AUC [tau] of Digoxin was reported.

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

    Time frame: 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: CL/F of Digoxin in plasma was reported.

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

    Time frame: 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: Cmax of Digoxin was reported.

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

    Time frame: 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: Tmax of Digoxin was reported.

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

    Time frame: 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: MRT of Digoxin was reported.

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

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

    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.

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

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

    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.

  9. PK: Renal Clearance (CLr) of Digoxin in Plasma

    Time frame: 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: CLr of Digoxin in plasma was reported.

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

    Time frame: 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: AUC[0-t] of Pirtobrutinib was reported.

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

    Time frame: 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: AUCtau of Pirtobrutinib was reported.

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

    Time frame: 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: CL/F of Pirtobrutinib in plasma was reported.

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

    Time frame: 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: Cmax of Pirtobrutinib was reported.

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

    Time frame: 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: Tmax of Pirtobrutinib was reported.

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

    Time frame: 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: MRT of Pirtobrutinib was reported.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Collaborators

  • Loxo Oncology, Inc.

Registry information

Official study title

A Phase I, Open-label, Fixed-sequence, Drug Interaction Study to Investigate the Effect of Single and Multiple Oral Doses of LOXO-305 on the Pharmacokinetics of Multiple Oral Doses of Digoxin (P-Glycoprotein Substrate) in Healthy Subjects

Important dates

Study start
2021
Primary completion
2021
Study completion
2021
First posted
Jan 8, 2024
Registry last updated
Feb 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.