A Drug Drug Interaction (DDI) Study of Pirtobrutinib (LOXO-305) and Digoxin (P-Glycoprotein Substrate) in Healthy Participants
- Registration Number
- NCT06194214
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
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- Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Digoxin + Pirtobrutinib Pirtobrutinib 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 Digoxin + Pirtobrutinib Digoxin 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
- Primary Outcome Measures
Name Time Method Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma 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.
PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma 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.
PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma 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.
PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma 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.
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma 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.
PK: Mean Residence Time (MRT) of Digoxin in Plasma 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.
PK: Cumulative Amount of Drug Excreted Unchanged in Urine (Ae) of Digoxin 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.
PK: Fraction of Digoxin Excreted Unchanged in Urine (Fe) Expressed as Percentage of Dose Excreted 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.
PK: Renal Clearance (CLr) of Digoxin in Plasma 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.
PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib in Plasma 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.
PK: Area Under the Concentration During a Dosing Interval (AUCtau) of Pirtobrutinib in Plasma 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.
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib in Plasma 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.
PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib in Plasma 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.
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib in Plasma 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.
PK: Mean Residence Time (MRT) of Pirtobrutinib in Plasma 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Covance Clinical Research Unit
🇺🇸Madison, Wisconsin, United States