Clinical trial NCT05338476: A Study of Effects of Selpercatinib (LY3527723) on Midazolam in Healthy Participants
Official title: An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of LOXO-292 on the Single Dose Pharmacokinetics of Midazolam in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Loxo Oncology, Inc.
First posted: 2022-04-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this study is to assess the effect of selpercatinib on how fast midazolam gets into the blood stream and how long it takes the body to remove it when administered in healthy participants. Information about safety and tolerability will be collected. The study will last up to about 6 weeks, inclusive of screening period.


Eligibility criteria: Inclusion Criteria :

* Male and female participants of non-childbearing potential who are agreeable to take birth control measures until study completion
* Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²) and had a minimum weight of at least 50 kg at screening
* Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study

Exclusion Criteria:

* Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study
* Have previously participated or withdrawn from this study
* Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study
* Had blood loss of more than 500 milliliters (mL) within the previous 30 days of study screening
* Require treatment with inducers or inhibitors of cytochrome P450 (CYP) CYP3A within 14 days before the first dose of study drug through the end of Period 2

Primary outcomes:
measure: Pharmacokinetics (PK): Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Midazolam
timeFrame: Days 1, 2, 10, and 11
measure: PK: Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of Midazolam
timeFrame: Days 1, 2, 10, and 11
measure: PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Midazolam
timeFrame: Days 1, 2, 10, and 11
measure: PK: Maximum observed concentration (Cmax) of Midazolam
timeFrame: Days 1, 2, 10, and 11
measure: PK: Time to reach Cmax (Tmax) of Midazolam
timeFrame: Days 1, 2, 10, and 11
measure: PK: Apparent first-order terminal elimination rate constant (Kel) of Midazolam
timeFrame: Days 1, 2, 10, and 11
measure: PK: Apparent first-order terminal elimination half-life (t½) of Midazolam
timeFrame: Days 1, 2, 10, and 11
measure: PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Midazolam
timeFrame: Days 1, 2, 10, and 11
measure: PK: Apparent volume of distribution during the terminal elimination phase (Vz/F) of Midazolam
timeFrame: Days 1, 2, 10, and 11
Secondary outcomes:
measure: PK : Area under the concentration-time curve, from time 0 to the 12 hour (AUC0-12) of Selpercatinib
timeFrame: Day 1
measure: PK: Area under the concentration-time curve during a dosing interval (tau) at steady state (AUCtau) of Selpercatinib
timeFrame: Days 1-11
measure: PK: Cmax of Selpercatinib
timeFrame: Days 1-11
measure: PK: Maximum observed concentration at steady-state (Cmax,ss) of Selpercatinib
timeFrame: Days 1-11
measure: PK: Concentration observed at the end of the dosing interval (Ctrough) of Selpercatinib
timeFrame: Days 1-11
measure: PK: Tmax of Selpercatinib
timeFrame: Days 1-11
measure: PK: Time to reach Cmax,ss (Tmax,ss) of Selpercatinib
timeFrame: Days 1-11
measure: PK: Apparent total plasma clearance (CL,ss/F) of Selpercatinib
timeFrame: Days 1-11
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: