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

Healthy Clinical Trial

Official title:

An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of LOXO-292 on the Single Dose Pharmacokinetics of Repaglinide in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05469113
• Other study ID #: 17754
• Secondary ID: J2G-OX-JZJSLOXO-
• Status: Completed
• Phase: Phase 1
• Start date: January 29, 2019
• Est. completion date: March 5, 2019

Study information

• Verified date: July 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to assess the effect of selpercatinib on how fast repaglinide 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 12 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: March 5, 2019
• Est. primary completion date: March 5, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 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

• Hemoglobin (Hb) A1c value < 6.5 % at screening and fasting glucose = 126 mg/dL.

• Males who are capable of fathering a child must agree to use one of the following methods of contraception from the time of the dose administration through 6 months after the last dose

• Female of non-childbearing potential only or must have undergone sterilization procedures at least 6months prior to the first dosing

Exclusion Criteria:

• History or presence of diabetes or history of prior episode(s) of hypoglycemia.

• Estimated creatinine clearance <90 mL/min at Screening or Check-in (Day -1, Period 1)

• Unable to refrain from or anticipates the use of any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements for 14 days prior to the first dosing and through EOT or ET. After first dosing, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the PI or designee

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Repaglinide
Administered orally.
• Selpercatinib
Administered orally.

Locations

Country	Name	City	State
United States	Celerion	Tempe	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (PK): Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Repaglinide	PK: AUC0-t of Repaglinide	Pre-dose up to 16 hours postdose
Primary	PK: Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of Repaglinide	PK: AUC0-inf of Repaglinide	Pre-dose up to 16 hours post-dose
Primary	PK: Percent of AUC0-inf extrapolated (AUC%extrap) of Repaglinide	PK: AUC%extrap of Repaglinide	Pre-dose up to 16 hours post-dose
Primary	PK: Maximum observed concentration (Cmax) of Repaglinide	PK: Cmax of Repaglinide	Pre-dose up to 16 hours post-dose
Primary	PK: Time to reach Cmax (Tmax) of Repaglinide	PK: Tmax of Repaglinide	Pre-dose up to 16 hour post-dose
Primary	PK: Apparent first-order terminal elimination rate constant (Kel) of Repaglindide	PK: Kel of Repaglindide	Pre-dose up to 16 hour post-dose
Primary	PK: Apparent first-order terminal elimination half-life (t½) of Repaglinide	PK: t½ of Repaglinide	Pre-dose up to 16 hour post-dose
Primary	PK: Apparent total plasma clearance after oral (extravascular) administration (CL/F) of Repaglinide	PK: CL/F of Repaglinide	Pre-dose up to 16 hour post-dose
Primary	PK: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F) of Repaglinide	PK: (Vz/F) of Repaglinide	Pre-dose up to 16 hour post-dose
Secondary	PK: Area under the concentration-time curve, from time 0 to the 12 hour timepoint (AUC0-12) of Selpercatinib (Day 1 of Period 2)	PK: AUC0-12 of Selpercatinib	Pre-morning dose up to 12 hours following the morning dose
Secondary	PK: Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of Selpercatinib (Day 1 of Period 2)	PK: AUC0-t of Selpercatinib	Pre-morning dose up to 12 hours following the morning dose
Secondary	PK: Maximum observed concentration (Cmax) of Selpercatinib (Day 1 of Period 2)	PK: Cmax of Selpercatinib	Pre-morning dose up to 12 hours following the morning dose
Secondary	PK: Time to reach Cmax (Tmax) of Selpercatinib (Day 1 of Period 2)	PK: Tmax of Selpercatinib	Pre-morning dose up to 12 hours following the morning dose
Secondary	PK: Area under the concentration-time curve during a dosing interval (tau) at steady state (AUCtau) of Selpercatinib (Day 10 of Period 2)	PK: AUCtau of Selpercatinib	Pre-morning dose up to 12 hours following the morning dose
Secondary	PK: Maximum observed concentration at steady-state (Cmax,ss) of Selpertcatinib (Day 10 of Period 2)	PK: Cmax,ss of Selpertcatinib	Pre-morning dose up to 12 hours following the morning dose
Secondary	PK: Concentration observed at the end of the dosing interval (Ctrough) of Selpercatinib (Day 10 of Period 2)	PK: Ctrough of Selpercatinib	Pre-morning dose
Secondary	PK: Time to reach Cmax,ss (Tmax,ss) of Selpercatinib (Day 10 of Period 2)	PK: Tmax,ss of Selpercatinib	Pre-morning dose up to 12 hours following the morning dose
Secondary	PK: Apparent total plasma clearance after oral (extravascular) administration(CL,ss/F) of Selpercatinib (Day 10 of Period 2)	PK: CL,ss/F of Selpercatinib	Pre-morning dose up to 12 hours following the morning dose