A Drug Drug Interaction (DDI) Study of Selpercatinib and Dabigatran in Healthy Participants

An Open-Label Study to Investigate the Effect of Selpercatinib on the Pharmacokinetics of Dabigatran in Healthy Volunteers

The main purpose of this study is to determine the effect of selpercatinib on the levels of dabigatran in the blood stream and how long it takes the body to remove dabigatran. This study will also look at how safe and well-tolerated of dabigatran when administered in combination with selpercatinib in healthy participants. This study will last approximately 22 to 25 days.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Selpercatinib; Drug: Dabigatran

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Overtly healthy males or females, as determined by medical history, physical examination and vital signs.
• Body mass index (BMI) within the range of 19 to 35 kilograms per meter squared (kg/m²)
• Male participants are not required to adhere to contraceptive requirements and female participants of childbearing potential must agree to be either remain abstinent or stay in a same sex relationship without sexual relationships with males or must agree to use a highly effective method of contraception and who underwent bilateral salpingectomy. The Female participants not of childbearing potential are not required to use contraception.

Exclusion Criteria:

• Have a positive pregnancy test at screening or Day -1, where applicable
• Are planning to become pregnant during the study or within 1 month of study completion
• Are women who are lactating
• Have known allergies to selpercatinib- or dabigatran-related compounds or any components of the formulation of selpercatinib or dabigatran, or history of significant atopy
• Have a history of allergic reactions to medications or food products
• Have a clinically significant abnormality of blood pressure and/or pulse rate as determined by the investigator
• Have known bleeding disorder including prior personal or familiar history of abnormal bleeding, hereditary or acquired coagulation or platelet disorder
• Clinically significant abnormalities on ECG as determined by the investigator or prolongation of the QTcB or QTcF >450 msec on more than 1 ECG obtained during screening only
• Have clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to the planned start of selpercatinib
• Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
• Have an average weekly alcohol intake that exceeds 21 units per week (males ≤65 years old) and 14 units per week (females); 1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirit(s)
• Are smokers of more than 10 cigarettes or e-cigarettes, or 3 cigars or 3 pipes, per day
• Consume excessive amounts of coffee, tea, cola, or other caffeinated beverages per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran + Selpercatinib; Participants received a single oral dose of 150 milligrams (mg) dabigatran on Day 1 and a single oral dose of 150 mg dabigatran coadministered with a single oral dose of 2 x 80 mg (160 mg) selpercatinib on Day 8. There was a washout period of 7 days between dosing on Days 1 and 8.	Drug: Selpercatinib; Administered orally.; Other Names: LY3527723; Drug: Dabigatran; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran	PK: Cmax of Dabigatran	Day 1 and Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours (h) postdose
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Dabigatran	PK: AUC(0-inf) of Dabigatran	Day 1 and Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Cmax of Selpercatinib	PK: Cmax of Selpercatinib	Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose
PK: AUC(0-inf) of Selpercatinib	PK: AUC(0-inf) of Selpercatinib	Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose
PK: Time of Maximum Observed Drug Concentration (Tmax) of Selpercatinib	PK: Tmax of Selpercatinib	Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose

Collaborators and Investigators

• Sponsor: Loxo Oncology, Inc.
• Collaborators: Eli Lilly and Company
• 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 record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Actual): May 17, 2021
• Study Completion (Actual): May 17, 2021

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 17972; J2G-MC-JZJV (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