Clinical trial NCT05469113: A Study of Effects of Selpercatinib (LY3527723) on Repaglinide 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 Repaglinide 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: 2022-07-21
Enrollment: 13
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 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.


Eligibility criteria: 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

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