A Study of Effects of Selpercatinib (LY3527723) on Midazolam in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05338476
• Collaborator: Loxo Oncology, Inc. (Industry)
• Enrollment: 16
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.2
• Patients Per Site Per Month: 7.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Midazolam; Drug: Selpercatinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: Jul 12, 2018
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Sep 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Midazolam Midazolam administered orally.	Drug: Midazolam; Administered orally.
Experimental: Selpercatinib and Midazolam Selpercatinib and midazolam administered orally.	Drug: Midazolam; Administered orally.; Drug: Selpercatinib; Administered orally.; Other Names: LY3527723 LOXO-292

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Midazolam [Days 1, 2, 10, and 11]

   PK: AUC0-t of Midazolam

2. PK: Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of Midazolam [Days 1, 2, 10, and 11]

   PK: AUC0-inf of Midazolam

3. PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Midazolam [Days 1, 2, 10, and 11]

   PK: AUC%extrap of Midazolam

4. PK: Maximum observed concentration (Cmax) of Midazolam [Days 1, 2, 10, and 11]

   PK: Cmax of Midazolam

5. PK: Time to reach Cmax (Tmax) of Midazolam [Days 1, 2, 10, and 11]

   PK: Tmax of Midazolam

6. PK: Apparent first-order terminal elimination rate constant (Kel) of Midazolam [Days 1, 2, 10, and 11]

   PK: Kel of Midazolam

7. PK: Apparent first-order terminal elimination half-life (t½) of Midazolam [Days 1, 2, 10, and 11]

   PK: t½ of Midazolam

8. PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Midazolam [Days 1, 2, 10, and 11]

   PK: CL/F of Midazolam

9. PK: Apparent volume of distribution during the terminal elimination phase (Vz/F) of Midazolam [Days 1, 2, 10, and 11]

   PK: Vz/F of Midazolam

Secondary Outcome Measures

1. PK : Area under the concentration-time curve, from time 0 to the 12 hour (AUC0-12) of Selpercatinib [Day 1]

   PK: AUC0-12 of Selpercatinib

2. PK: Area under the concentration-time curve during a dosing interval (tau) at steady state (AUCtau) of Selpercatinib [Days 1-11]

   AUCtau of Selpercatinib

3. PK: Cmax of Selpercatinib [Days 1-11]

   PK: Cmax of Selpercatinib

4. PK: Maximum observed concentration at steady-state (Cmax,ss) of Selpercatinib [Days 1-11]

   PK: Cmax,ss of Selpercatinib

5. PK: Concentration observed at the end of the dosing interval (Ctrough) of Selpercatinib [Days 1-11]

   PK: Ctrough of Selpercatinib

6. PK: Tmax of Selpercatinib [Days 1-11]

   PK: Tmax of Selpercatinib

7. PK: Time to reach Cmax,ss (Tmax,ss) of Selpercatinib [Days 1-11]

   PK: Tmax,ss of Selpercatinib

8. PK: Apparent total plasma clearance (CL,ss/F) of Selpercatinib [Days 1-11]

   PK: CL,ss/F of Selpercatinib

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion	Tempe	Arizona	United States	85283

Sponsors and Collaborators

• Eli Lilly and Company
• Loxo Oncology, Inc.

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT05338476
• Other Study ID Numbers: 17753; J2G-OX-JZJR; LOXO-RET-18017
• First Posted: Apr 21, 2022
• Last Update Posted: Apr 21, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Midazolam

Study Results

No Results Posted as of Apr 21, 2022