Study of Pirtobrutinib (LOXO-305) in Participants With Impaired Liver Function and Healthy Participants

Healthy Clinical Trial

Official title:

An Open-label, Nonrandomized, Single-dose, Parallel-group, Safety, Tolerance, and Pharmacokinetic Study of LOXO-305 Administered to Fasted Hepatically Impaired Male and Female Subjects and Fasted Matched-control Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06190691
• Other study ID #: LOXO-BTK-20012
• Secondary ID: J2N-OX-JZNF
• Status: Completed
• Phase: Phase 1
• Start date: December 18, 2020
• Est. completion date: December 30, 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and/or Sponsor:

1. pancreatitis

2. peptic ulcer disease

3. intestinal malabsorption

4. gastric reduction surgery

5. history or presence of clinically significant cardiovascular disease.

• Participants with out-of-range, at-rest vital signs.

• Abnormal laboratory values determined to be clinically significant by the Investigator (or designee).

• Clinically significant abnormality, as determined by the Investigator (or designee), from physical examination.

• 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).

• 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.

• 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.

• Donation of blood from 56 days prior to Screening, plasma or platelets from 4 weeks prior to Screening.

• Receipt of blood products within 2 months prior to Check-in (Day -1).

• 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).

Related Conditions & MeSH terms

• Healthy
• Hepatic Insufficiency
• Liver Failure

Intervention

Drug:
• Pirtobrutinib
Administered orally

Locations

Country	Name	City	State
United States	Orange County Research Institute	Anaheim	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	Orlando Clinical Research Center	Orlando	Florida
United States	Pinnacle Clinical Research	San Antonio	Texas
United States	The Texas Liver Institute	San Antonio	Texas
United States	Orange County Research Center	Tustin	California

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): Maximum Observed Concentration (Cmax) of Pirtobrutinib	PK: Cmax of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib	PK: Tmax of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Area Under the Concentration-time Curve, From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib	PK: AUC0-t of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Area Under the Concentration-time Curve, From Hour 0 to Infinity (AUC0-inf) of Pirtobrutinib	PK: AUC0-inf of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Percentage extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib	PK: %AUCextrap of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Apparent Terminal Elimination Rate Constant (?Z) of Pirtobrutinib	PK: ?Z of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib	PK: t½ of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib	PK: CL/F of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib	PK: Vz/F of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Mean Residence Time (MRT) of Pirtobrutinib	PK: MRT of pirtobrutinib	Pre-dose up to 168 hours post-dose
Primary	PK: Unbound Cmax (Cmax,u) of Pirtobrutinib	PK: Cmax,u of pirtobrutinib	Predose (Within 30 mins prior to dosing) on Day 1
Primary	PK: Unbound AUC0-t (AUC0-t,u) of Pirtobrutinib	PK: AUC0-t,u of pirtobrutinib	Predose (Within 30 mins prior to dosing) on Day 1
Primary	PK: Unbound AUC0-inf (AUC0-inf,u) of Pirtobrutinib	PK: AUC0-inf,u of pirtobrutinib	Predose (Within 30 mins prior to dosing) on Day 1
Primary	PK: Unbound CL/F (CL/F,u) of Pirtobrutinib	PK: CL/F,u of pirtobrutinib	Predose (Within 30 mins prior to dosing) on Day 1
Primary	PK: Unbound Vz/F (Vz/F,u) of Pirtobrutinib	PK: Vz/F,u of pirtobrutinib	Predose (Within 30 mins prior to dosing) on Day 1