Study of Pirtobrutinib (LOXO-305) in Participants With Impaired Liver Function and Healthy Participants
- Registration Number
- NCT06190691
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The main purpose of this study is to measure how much of pirtobrutinib (LOXO-305) gets into the bloodstream and how long it takes the body to eliminate it in participants with impaired liver function and healthy participants. The side effects and tolerability of pirtobrutinib will also be evaluated. Participation could last about 46 days.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
- Participants with mild, moderate or severe hepatic impairment and healthy participants with normal hepatic function
- Males and females of non-childbearing potential.
- Within body mass index (BMI) range 18.5 to 40.0 kilograms per square meter (kg/m²).
- Participants will be in good health, based on medical history, physical examination findings, vital signs, 12 lead electrocardiogram (ECG), and clinical laboratory tests, as determined by the Investigator (or designee).
- Able to comply with all study procedures, including the 8-night stay at the Clinical Research Unit and follow-up phone call.
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History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and/or Sponsor:
- pancreatitis
- peptic ulcer disease
- intestinal malabsorption
- gastric reduction surgery
- history or presence of clinically significant cardiovascular disease.
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Participants with out-of-range, at-rest vital signs.
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Abnormal laboratory values determined to be clinically significant by the Investigator (or designee).
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Clinically significant abnormality, as determined by the Investigator (or designee), from physical examination.
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Participation in any other investigational study drug trial involving administration of any investigational drug in the past 30 days or 5 half-lives, whichever was longer, prior to the first dose administration (Day 1).
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Use or intention to use any prescription or over-the-counter medications within 14 days prior to the first dose administration (Day 1) and through end of trial.
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History or presence, upon clinical evaluation, of any illness that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results, or put the participant at undue risk.
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Donation of blood from 56 days prior to Screening, plasma or platelets from 4 weeks prior to Screening.
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Receipt of blood products within 2 months prior to Check-in (Day -1).
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Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, biliary, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the Investigator).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pirtobrutinib (Normal Hepatic Function) Pirtobrutinib Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1. Pirtobrutinib (Mild Hepatic Impairment) Pirtobrutinib Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1. Pirtobrutinib (Moderate Hepatic Impairment) Pirtobrutinib Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1. Pirtobrutinib (Severe Hepatic Impairment) Pirtobrutinib Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
- Primary Outcome Measures
Name Time Method Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: Cmax of pirtobrutinib
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: Tmax of pirtobrutinib
PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: AUC0-t of pirtobrutinib
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: AUC0-inf of pirtobrutinib
PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: %AUCextrap of pirtobrutinib
PK: Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: t½ of pirtobrutinib
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: CL/F of pirtobrutinib
PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: Vz/F of pirtobrutinib
PK: Mean Residence Time (MRT) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) MRT is the average time a drug molecule stays in the body, calculated from the AUC0-inf.
PK: Unbound Cmax (Cmax,u) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) Cmax,u was calculated by multiplying Cmax by Fu (i.e., Cmax\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
PK: Unbound AUC0-t (AUC0-t,u) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) AUC0-t,u was calculated by multiplying AUC0-t by Fu (i.e., AUC0-t\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
PK: Unbound AUC0-inf (AUC0-inf,u) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) AUC0-inf,u was calculated by multiplying AUC0-inf by Fu (i.e., AUC0-inf\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
PK: Unbound CL/F (CL/F,u) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) CL/F,u was calculated by multiplying CL/F by Fu (i.e., CL/F\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
PK: Unbound Vz/F (Vz/F,u) of Pirtobrutinib Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) Vz/F,u was calculated by multiplying Vz/F by Fu (i.e., Vz/F\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function) Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: λZ of pirtobrutinib
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function) Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: λZ of pirtobrutinib
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function) Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: λZ of pirtobrutinib
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Severe Hepatic Function) Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose) PK: λZ of pirtobrutinib
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (8)
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States
Pinnacle Clinical Research
🇺🇸San Antonio, Texas, United States
Orange County Research Institute
🇺🇸Anaheim, California, United States
Orange County Research Center
🇺🇸Tustin, California, United States
Riverside Clinical Research
🇺🇸Edgewater, Florida, United States
Advanced Pharma Clinical Research
🇺🇸Miami, Florida, United States
Clinical Pharmacology of Miami
🇺🇸Miami, Florida, United States
The Texas Liver Institute
🇺🇸San Antonio, Texas, United States