Clinical trial
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
Name
LOXO-BTK-20021
Description
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 arms
Trial start
2021-03-11
Estimated PCD
2021-06-09
Trial end
2021-06-09
Status
Completed
Phase
Early phase I
Treatment
Pirtobrutinib
Administered Orally.
Arms:
Pirtobrutinib
Other names:
LOXO-305, LY3527727
Digoxin
Administered Orally.
Arms:
Digoxin
Size
16
Primary endpoint
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Eligibility criteria
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
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 16, 'type': 'ACTUAL'}}
Updated at
2024-01-08
1 organization
2 products
1 indication
Organization
Eli Lilly and CompanyProduct
DigoxinIndication
HealthyProduct
Pirtobrutinib