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

NCT05134337 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: LOXO-BTK-20006J2N-OX-JZNC
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (7)

• 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

Study Arms (2)

Part 1 (LOXO-305/Itraconazole)

EXPERIMENTAL

* 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; Drug: Itraconazole

Part 2 (LOXO 305/Rifampin)

EXPERIMENTAL

* 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; Drug: Rifampin

Interventions

LOXO-305 DRUG

Oral LOXO-305

Also known as: Pirtobrutinib

Part 1 (LOXO-305/Itraconazole); Part 2 (LOXO 305/Rifampin)

Itraconazole DRUG

Oral itraconazole

Part 1 (LOXO-305/Itraconazole)

Rifampin DRUG

Oral rifampin

Part 2 (LOXO 305/Rifampin)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Loxo Oncology, Inc.: lead

Study Sites (1)

Covance Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

MeSH Terms

Interventions

pirtobrutinib; Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• Renée Ward, MD, PhD

  Loxo Oncology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2021
• First Posted: November 24, 2021
• Study Start: February 12, 2020
• Primary Completion: October 30, 2020
• Study Completion: October 30, 2020
• Last Updated: January 9, 2025
• Results First Posted: January 9, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)