NCT06180967

Brief Summary

The main purpose of this study is to assess the effect of Pirtobrutinib (LOXO-305) on how fast different formulations of midazolam gets into the blood stream and how long it takes the body to remove it when administered in healthy participants. The study will also access how much endogenous coproporphyrins I and III as biomarkers of OATP1B1 and OATP1B3 is in the bloodstream and how the body handles and eliminates them following single and multiple oral doses of Pirtobrutinib. Safety and tolerability of Pirtobrutinib will also be evaluated. For each participant, the total duration of the study will be 59 days, including screening.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1 healthy

Timeline
Completed

Started Sep 2020

Shorter than P25 for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 3, 2020

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 20, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 20, 2020

Completed
3.1 years until next milestone

First Submitted

Initial submission to the registry

December 13, 2023

Completed
13 days until next milestone

First Posted

Study publicly available on registry

December 26, 2023

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

February 24, 2025

Completed
Last Updated

February 24, 2025

Status Verified

January 1, 2025

Enrollment Period

2 months

First QC Date

December 13, 2023

Results QC Date

January 31, 2025

Last Update Submit

January 31, 2025

Conditions

Healthy

Outcome Measures

Primary Outcomes (19)

  • Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam) Following Oral Dose Administration

    PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Area Under the Concentration-Time From Time 0 Extrapolated To Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration

    PK: AUC(0-inf) of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration

    PK: %AUCextrap of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Maximum Observed Plasma Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration

    PK: Cmax of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration

    PK: tmax of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Apparent Terminal Elimination Rate Constant (Lambda [λ] z) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration

    PK: λz of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Apparent Systemic Clearance (CL/F) of Midazolam Following Oral Dose Administration

    PK: CL/F of midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Apparent Volume of Distribution (Vz/F) of Midazolam Following Oral Dose Administration

    PK: Vz/F of midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Apparent Plasma Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration

    PK: t½ of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.

    Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Total Clearance (CL) of Midazolam Following Intravenous Dose Administration

    PK: CL of midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Volume of Distribution (Vz) of Midazolam Following Intravenous Dose Administration

    PK: Vz of midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Volume of Distribution at Steady State (Vss) of Midazolam Following Intravenous Dose Administration

    PK: Vss of midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration

    PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Area Under the Concentration-Time From Time 0 Extrapolated To Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration

    PK: AUC0-inf of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration

    PK: %AUCextrap of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Maximum Observed Plasma Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration

    PK: Cmax of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration

    PK: tmax of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Apparent Terminal Elimination Rate Constant (λz) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration

    PK: λz of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

  • PK: Apparent Plasma Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration

    PK: t1/2 of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.

    Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)

Secondary Outcomes (7)

  • PK: Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib

    Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)

  • PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib

    Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)

  • PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib

    Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)

  • PK: Concentration Observed at the End Of the Dosing Interval (Ctrough) of Pirtobrutinib

    Period 2: 24-hour post-dose on Day 14, Day 15, and Day 17

  • PK: Time To Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib

    Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)

  • +2 more secondary outcomes

Study Arms (3)

Midazolam (Intravenous [IV] Bolus)

EXPERIMENTAL

A single IV bolus dose of midazolam will be administered in the morning following a 10-hour fast prior to dosing and a 4-hour fast postdose on Day 1 and Day 15.

Drug: Midazolam Solution

Midazolam Oral

EXPERIMENTAL

A single oral dose of midazolam will be administered in the morning following a 10-hour fast prior to dosing and a 4-hour fast postdose on Day 3 and Day 17.

Drug: Midazolam Syrup

Pirtobrutinib

EXPERIMENTAL

Multiple oral doses of Pirtobrutinib once a day (QD) will be administered on Days 5 through Day 17.

Drug: Pirtobrutinib

Interventions

Midazolam SyrupDRUG

Administered Orally.

Midazolam Oral
Midazolam SolutionDRUG

Administered IV bolus.

Midazolam (Intravenous [IV] Bolus)
PirtobrutinibDRUG

Administered Orally.

Also known as: LOXO-305, LY3527727
Pirtobrutinib

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive
  • Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator
  • Female participants of non-childbearing potential and male participants who follow standard contraceptive methods
  • Must have comply with all study procedures, including the 8-night stay at the Clinical Research Unit (CRU) and follow-up phone call

You may not qualify if:

  • History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor
  • Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus immunoglobulin M (HBV IgM) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening
  • Positive polymerase chain reaction (PCR) test for COVID-19 at Screening or Check-in (Day -1)
  • Known ongoing alcohol and/or drug abuse within 2 years prior to Screening
  • History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee)
  • Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Covance Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

MeSH Terms

Interventions

pirtobrutinib

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company
ClinicalTrials.gov@lilly.com
08005455979

Study Officials

  • Renee 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

December 13, 2023

First Posted

December 26, 2023

Study Start

September 3, 2020

Primary Completion

October 20, 2020

Study Completion

October 20, 2020

Last Updated

February 24, 2025

Results First Posted

February 24, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)