Study of the Effects of Itraconazole and Rifampin on LOXO-305 in Healthy Participants

A Phase 1, Open Label, Two-part, Fixed-sequence Drug Interaction Study to Investigate the Effect of Strong CYP3A4 Inhibitor (Itraconazole) and CYP3A4 Inducer (Rifampin) on the Pharmacokinetics of LOXO 305 in Healthy Adult Subjects

The main purpose of this study is to learn about how itraconazole and rifampin affect LOXO-305 in healthy participants. Participation could last about 8 weeks.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: LOXO-305; Drug: Itraconazole; Drug: Rifampin

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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).
• Able to comply with all study procedures, including the 19-night stay for those participating in Part 1 or 24-night stay for those participating in Part 2 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:

  • liver disease
  • pancreatitis
  • peptic ulcer disease
  • intestinal malabsorption
  • gastric reduction surgery
  • 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), or cancer within the past 5 years (except localized basal cell, squamous, or in situ cancer of the skin).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (LOXO-305/Itraconazole); Day 1: a single oral dose of 200 milligrams (mg) LOXO-305 was administered.; Day 8: oral doses of 200 mg itraconazole was administered twice daily.; Days 9 to 18: single oral dose of 200 mg itraconazole was administered once daily, and on Day 12 it was co-administered with a single oral dose of 200 mg LOXO-305.	Drug: LOXO-305; Oral LOXO-305; Other Names: Pirtobrutinib; Drug: Itraconazole; Oral itraconazole
Experimental: Part 2 (LOXO 305/Rifampin); Day 1: a single oral dose of 200 mg LOXO-305 was administered.; Days 8 to 23: oral dose of 600 mg rifampin was administered once daily, and on Days 8 & 17, it was co-administered with a single oral dose of 200 mg LOXO-305.	Drug: LOXO-305; Oral LOXO-305; Other Names: Pirtobrutinib; Drug: Rifampin; Oral rifampin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305	Cmax of LOXO-305	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 on days 1 and 12
Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305	PK: AUC0-t of LOXO 305	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 on days 1 and 12
Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305	AUC0-inf of LOXO-305	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 on days 1 and 12
Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305	Cmax of LOXO-305	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 on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305	PK: AUC0-t of LOXO 305	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 on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305	AUC0-inf of LOXO-305	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 on days 1 and 17
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of LOXO-305	AUC0-24 of LOXO-305	Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on days 1 and 8

Collaborators and Investigators

• Sponsor: Loxo Oncology, Inc.
• Investigators: Study Director: Renee Ward, MD, PhD, Loxo Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2020
• Primary Completion (Actual): October 30, 2020
• Study Completion (Actual): October 30, 2020

Study Registration Dates

• First Submitted: October 22, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Tyrosine Kinase Inhibitors; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Cytochrome P-450 CYP3A Inhibitors; Leprostatic Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Pirtobrutinib; Rifampin; Itraconazole
• Other Study ID Numbers: LOXO-BTK-20006; J2N-OX-JZNC (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No