A Study of Effect of Selpercatinib (LY3527723) on Corrected QT (QTc) Interval in Healthy Participants

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Selpercatinib
Drug: Moxifloxacin
Drug: Placebo

Registration Number: NCT05630274

Lead Sponsor: Eli Lilly and Company

Brief Summary: The main purpose of this study is to assess the effect of Selpercatinib (LY3527723) on the heart rate-corrected QT (QTc) interval. The study will last up to 41 days.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

Inclusion Criteria

Healthy, adult, non-smoking, male or female (of non childbearing potential only or undergone sterilization procedures at least 6 months prior to the Screening) with no ECG abnormalities.
Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²) at Screening and have a minimum weight of at least 50 kg at Screening
Female of non childbearing potential: must have undergone sterilization procedures at least 6 months prior to the Screening
Males who are capable of fathering a child must agree to use contraception from the time of the dose administration through 6 months after the last dose

Exclusion Criteria

Estimated creatinine clearance <90 milliliter per minute (mL/min) at Screening or Check in (Day -1; rechecks will be permitted up to two times to confirm participant eligibility for study participation).
Has serum potassium levels <3.8 milliequivalents per liter (mEq/L) at Screening or Check in (Day -1; rechecks will be permitted up to two times to confirm participant eligibility for study participation).
Has serum calcium levels < 8.5 milligrams/deciliter (mg/dL) at Screening or Check in (Day -1; rechecks will be permitted up to two times to confirm participant eligibility for study participation).
Has serum magnesium levels <2.0 mEq/L at Screening or Check in (Day -1; rechecks will be permitted up to two times to confirm participant eligibility for study participation)

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence 1: ABCD	Selpercatinib	Period 1: 320 milligram (mg) Selpercatinib and Selpercatinib matching placebo (Treatment A) Period 2: 640 mg Selpercatinib (Treatment B) Period 3: 400 mg moxifloxacin (Treatment C) Period 4: Selpercatinib matching placebo (Treatment D) Participants received their assigned treatments in each of the above treatment period on Day 1 orally.
Treatment Sequence 2: BDAC	Selpercatinib	Period 1: 640 mg Selpercatinib (Treatment B) Period 2: Selpercatinib matching placebo (Treatment D) Period 3: 320 mg Selpercatinib and Selpercatinib matching placebo (Treatment A) Period 4: 400 mg moxifloxacin (Treatment C) Participants received their assigned treatments in each of the above treatment period on Day 1 orally.
Treatment Sequence 3: CADB	Moxifloxacin	Period 1: 400 mg moxifloxacin (Treatment C) Period 2: Selpercatinib matching placebo (Treatment D) Period 3: 320 mg Selpercatinib and Selpercatinib matching placebo (Treatment A) Period 4: 640 mg Selpercatinib (Treatment B) Participants received their assigned treatments in each of the above treatment period on Day 1 orally. Period Title: Treatment Period 1
Treatment Sequence 4: DCBA	Placebo	Period 1: Selpercatinib matching placebo (Treatment D) Period 2: 400 mg moxifloxacin (Treatment C) Period 3: 640 mg Selpercatinib (Treatment B) Period 4: 320 mg Selpercatinib and Selpercatinib matching placebo (Treatment A) Participants received their assigned treatments in each of the above treatment period on Day 1 orally.

Primary Outcome Measures

Name	Time	Method
Cardiodynamics: Placebo-corrected Change From Baseline in QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF) for Treatments A, B, and C	Pre-dose, -0.25, -0.5, -0.25, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, and 24 hours post-dose	The cardiodynamic assessment was performed through 12-lead electrocardiogram (ECG) extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF. Placebo-corrected change from baseline in QTcF (ΔΔQTcF) was calculated based on model-predicted effect
Pharmacokinetics (PK): Area Under the Concentration-time Curve From Time 0 to the Time of the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib	Pre-dose, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose	PK: AUC0-t of Selpercatinib is reported.
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib	Pre-dose, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose	PK: AUC0-inf of Selpercatinib is reported.
PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib	Pre-dose, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose	PK: AUC%extrap of Selpercatinib is reported.
PK: Time to Reach Cmax (Tmax) of Selpercatinib	Pre-dose, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose	PK: Tmax of Selpercatinib is reported.
PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib	Pre-dose, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose	PK: Kel of Selpercatinib is reported.
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib	Pre-dose, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose	PK: t½ of Selpercatinib is reported.
PK: Maximum Observed Concentration (Cmax) of Selpercatinib	Pre-dose, 0.25, 0.5, 0.75, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose	PK: Cmax of Selpercatinib is reported.