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

Healthy Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06194214
• Other study ID #: LOXO-BTK-20021
• Secondary ID: J2N-OX-JZNT
• Status: Completed
• Phase: Phase 1
• Start date: March 11, 2021
• Est. completion date: June 9, 2021

Study information

• Verified date: January 2024
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 9, 2021
• Est. primary completion date: June 9, 2021
• 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 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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Pirtobrutinib
Administered Orally.
• Digoxin
Administered Orally.

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit	Madison	Wisconsin

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 (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Digoxin		Predose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Days 7, 8, and 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Area Under the Concentration During a Dosing Interval (AUCtau): Digoxin		Predose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Days 7, 8, and 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Apparent Systemic Clearance (CL/F): Digoxin		Predose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Days 7, 8, and 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Maximum Observed Plasma Concentration (Cmax): Digoxin		Predose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Days 7, 8, and 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Time to Maximum Observed Plasma Concentration (Tmax): Digoxin		Predose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Days 7, 8, and 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Mean Residence Time (MRT): Digoxin		Predose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Days 7, 8, and 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Amount of Drug Excreted Unchanged in Urine (Ae): Digoxin		Within 12 hours prior to dose administration (-12 to 0 hours predose) and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose on Day 7 and Day 16
Primary	PK: Fraction of Drug Excreted Unchanged in Urine (Fe): Digoxin		Within 12 hours prior to dose administration (-12 to 0 hours predose) and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose on Day 7 and Day 16
Primary	PK: Renal Clearance (CLr): Digoxin		Within 12 hours prior to dose administration (-12 to 0 hours predose) and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose on Day 7 and Day 16
Primary	PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t): Pirtobrutinib		Pre dose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Day 8 and Day 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Area Under the Concentration During a Dosing Interval (AUCtau): Pirtobrutinib		Pre dose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Day 8 and Day 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Apparent Systemic Clearance (CL/F): Pirtobrutinib		Pre dose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Day 8 and Day 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Maximum Observed Plasma Concentration (Cmax): Pirtobrutinib		Pre dose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Day 8 and Day 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Time to Maximum Observed Plasma Concentration (Tmax): Pirtobrutinib		Pre dose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Day 8 and Day 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20
Primary	PK: Mean Residence Time (MRT): Pirtobrutinib		Pre dose (within 30 minutes of dosing) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose on Day 8 and Day 16, and at 48, 72, and 96 hours postdose on Day 16 and/or Day 20