A Safety Study of LY3493269 in Healthy Participants

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: LY3493269
Drug: Placebo

Registration Number: NCT04498390

Lead Sponsor: Eli Lilly and Company

Brief Summary: The main purpose of this study in healthy participants is to learn more about the safety of LY3493269 and any side effects that might be associated with it. Blood tests will be performed to check how much LY3493269 gets into the bloodstream and how long it takes the body to eliminate it. For each participant, the study will last about 10 weeks and may include 12 visits, including five nights in a row in the clinical research center.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

Inclusion Criteria

Are male or female not of childbearing potential
Body mass index within the range of 19.0 to 40.0 kilograms per square meter (kg/m²) (inclusive)
Participants who are healthy as determined through medical evaluation including screening medical history, physical examination, vital signs, clinical laboratory tests, and electrocardiogram (ECG)
Have clinical laboratory test results within normal reference range for the population or clinical research unit (CRU), or results with acceptable deviations that are judged to be not clinically significant by the investigator
Have glycated hemoglobin level of less than (<)6.5 percent (%)

Exclusion Criteria

Have a supine heart rate (HR) less than 50 beats per minute (bpm) or greater than 100 bpm. If a repeat measurement shows values within the range, the participant can be included in the trial
Have a mean supine systolic blood pressure (BP) higher than 160 millimeters of Mercury (mmHg) and a mean supine diastolic BP higher than 95 mmHg from 2 assessments at screening (excluding white-coat hypertension); therefore, if a repeated measurement shows values within the range, the participant can be included in the trial
Have undergone any form of bariatric surgery
Have a history of gastrointestinal (GI) bleeding or duodenal ulcers
Have a personal or family history of medullary thyroid carcinoma or have multiple endocrine neoplasia syndrome type 2
Have a history of acute or chronic pancreatitis, or elevation in serum lipase and/or amylase levels greater than 1.5 times the upper limit of normal (ULN)
Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis
Have been treated with prescription drugs that promote weight loss within 3 months prior to screening
Have participated within the past 30 days of screening in a clinical study involving an investigational product (IP); at least 5 half-lives or 30 days, whichever is longer, should have passed
Have an abnormality in the 12-lead ECG at screening that, in the opinion of the investigator, increases the risks associated with participating in the study or may confound ECG (QT) data analysis, such as a QT interval corrected using Fridericia's formula (QTcF) greater than (>)450 milliseconds (msec) for males and >470 msec for females, short PR interval (<120 msec), or PR interval >220 msec, second and third atrioventricular block, intraventricular conduction delay with QRS >120 msec, right bundle branch block, left bundle branch block or Wolff-Parkinson-White syndrome
Have serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times (X) ULN or total bilirubin level (TBL) >1.5X ULN
Have known allergies to LY3493269, related compounds, or any components of the formulation (including C10), or a history of significant atopy

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LY3493269	LY3493269	8, 24 or 48 milligrams (mg) LY3493269 + 250 or 500 mg permeation enhancer sodium caprate(C10) Once daily (QD) administered orally over 3 consecutive study days.
Placebo	Placebo	Placebo administered orally over 3 consecutive study days.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Baseline through Day 43	An SAE is an adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.

Secondary Outcome Measures

Name	Time	Method
PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses	Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and Day 2 predose; Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose, Day 4, pre-dose	PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC\[0-24\]) of LY3493269 From Day 1 and Day 3 Doses Note: 1. 24 hour timepoint for Day 1 is the Day 2 pre-dose timepoint, which is the reason why Day 2 pre-dose is included in the timeframe. 2. 24 hour timepoint for Day 3 is the Day 4 pre-dose timepoint, which is the reason why Day 4 pre-dose is included in the timeframe.
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses	Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 2. 6, 8, 12 and Day 2 predose; Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose, Day 4, pre-dose	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269. Note: 1. 24 hour timepoint for Day 1 is the Day 2 pre-dose timepoint, which is the reason why Day 2 pre-dose is included in the timeframe. 2. 24 hour timepoint for Day 3 is the Day 4 pre-dose timepoint, which is the reason why Day 4 pre-dose is included in the timeframe.