A Study of Two Different Formulations of Pirtobrutinib (LOXO-305) In Healthy Participants

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Pirtobrutinib

Registration Number: NCT06258174

Lead Sponsor: Eli Lilly and Company

Brief Summary: The main purpose of this study is to compare two different formulations (mixtures) of pirtobrutinib (LOXO-305) in healthy participants. This study will compare how much of each formulation gets into the blood stream and how long it takes the body to remove it. Information about any side effects that may occur will be collected. The study will last up to 65 days.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

Inclusion Criteria

Males and females of non-childbearing potential.
Within body mass index (BMI) range 18.0 to 32.0 kilograms per square meter (kg/m²).
Participants will be in good general health, based on medical history, physical examination findings, vital signs, 12 lead electrocardiogram (ECG), or clinical laboratory tests, as determined by the Investigator (or designee).

Exclusion Criteria

History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and/or Sponsor:
1. liver disease
2. pancreatitis
3. peptic ulcer disease
4. intestinal malabsorption
5. cholecystectomy
6. gastric reduction surgery
7. 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 Day 1.
Use or intention to use any prescription or over-the-counter medications within 14 days prior to 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), or cancer within the past 5 years (except localized basal cell, squamous, or in situ cancer of the skin).

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
200 mg Pirtobrutinib (Sequence R/T)	Pirtobrutinib	Period 1: Participants received a reference formulation (R) of oral pirtobrutinib 200 milligrams (mg) on day 1. Period 2: Participants received a test formulation (T) of oral pirtobrutinib 200 mg on day 8. There was a washout period of 7 days between the doses of pirtobrutinib.
200 mg Pirtobrutinib (Sequence T/R)	Pirtobrutinib	Period 1: Participants received a test formulation (T) of oral pirtobrutinib 200 mg on day 1. Period 2: Participants received a reference formulation (R) of oral pirtobrutinib 200 mg on day 8. There was a washout period of 7 days between the doses of pirtobrutinib.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib	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: AUC0-24 of Pirtobrutinib
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib	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 Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib	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: t1/2 of Pirtobrutinib
PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib	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: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib	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	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	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: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib	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: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib	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 Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib	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