Phase 1
Completed N=16
A Drug Drug Interaction (DDI) Study of Pirtobrutinib (LOXO-305) and Digoxin (P-Glycoprotein Substrate) in Healthy Participants
Healthy
Source: ClinicalTrials.gov NCT06194214 ↗
Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Feb 2025
Primary outcomePrimary: Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma — 14.6; 17.1; 48.9 hour*nanogram per milliliter (h*ng/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma |
14.6; 17.1; 48.9 | — |
| PRIMARY PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma |
14.7; 17.2; 20.4 | — |
| PRIMARY PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma |
17.0; 14.5; 12.2 | — |
| PRIMARY PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma |
1.57; 2.38; 2.45 | — |
| PRIMARY PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma |
1.27; 1.25; 1.00 | — |
| PRIMARY PK: Mean Residence Time (MRT) of Digoxin in Plasma |
52.2; 65.2; 60.4 | — |
| PRIMARY PK: Cumulative Amount of Drug Excreted Unchanged in Urine (Ae) of Digoxin |
0.123; 0.148 | — |
| PRIMARY PK: Fraction of Digoxin Excreted Unchanged in Urine (Fe) Expressed as Percentage of Dose Excreted |
49.2; 59.4 | — |
| PRIMARY PK: Renal Clearance (CLr) of Digoxin in Plasma |
8.35; 7.28 | — |
| PRIMARY PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib in Plasma |
48400; 189000 | — |
| PRIMARY PK: Area Under the Concentration During a Dosing Interval (AUCtau) of Pirtobrutinib in Plasma |
48600; 106000 | — |
| PRIMARY PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib in Plasma |
1.89 | — |
| PRIMARY PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib in Plasma |
4330; 7530 | — |
| PRIMARY PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib in Plasma |
2.50; 2.50 | — |
| PRIMARY PK: Mean Residence Time (MRT) of Pirtobrutinib in Plasma |
22.6; 30.5 | — |
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
Data sourced from ClinicalTrials.gov (NCT06194214). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.