Clinical trial NCT05794243: A Multiple-Dose Study of LY3493269 in Healthy Participants
Official title: An Open-Label, Multiple-Dose Study to Investigate the Pharmacokinetics of LY3493269 Oral Formulations Administered in a Fed or Fasted State in Healthy Participants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2023-04-03
Enrollment: 42
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this study is to conduct blood tests to measure how much LY3493269 is in the bloodstream and how the body handles and eliminates LY3493269 when administered orally as test compared to reference formulations in healthy participants in fed and/or fasted states. The study will also evaluate the safety and tolerability of LY3493269 in these participants. The study will last up to 43 days excluding the screening period.


Eligibility criteria: Inclusion Criteria:

* Male or female participants who are overtly healthy as determined by medical evaluation
* Participants with body mass index (BMI) of 19.0 to 40.0 kilograms per meter squared (kg/m²)
* Males who agree to use highly effective/effective methods of contraception and only women not of childbearing potential may participate in the trial

Exclusion Criteria:

* Have a history of atopy (severe or multiple allergic manifestations) or clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, anaphylaxis, angioedema, or exfoliative dermatitis)
* Have a significant history of or current cardiovascular (for example, myocardial infarction, congestive heart failure, cerebrovascular accident, venous thromboembolism, etc.), respiratory, renal, gastrointestinal (GI) including involving the liver, gallbladder or gallbladder surgery, endocrine, hematological (including history of thrombocytopenia), or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk while taking the investigational product (IP); or of interfering with the interpretation of data.
* Have a mean supine heart rate (HR) less than 45 bpm or greater than 100 bpm from 2 assessments at screening.
* Have a mean supine systolic blood pressure (BP) higher than 160 mmHg and a mean supine diastolic BP higher than 95 mmHg from 2 assessments at screening
* Have undergone any form of bariatric surgery.
* Have a history of GI bleeding, or gastric or duodenal ulcers.
* Have a personal or family history of medullary thyroid carcinoma or 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 clinical signs or symptoms of liver disease, acute or chronic hepatitis.
* Have evidence of significant active neuropsychiatric disease as determined by the investigator.
* Have been treated with prescription drugs that promote weight loss within 3 months prior to screening.
* Are currently enrolled in a clinical study involving an IP or any other type of medical research judged not to be scientifically or medically compatible with this study.
* Have participated within the past 30 days of screening in a clinical study involving an IP; at least 5 half-lives or 30 days, whichever is longer, should have passed.
* Have an abnormality in the 12-lead electrocardiogram (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) \>450 msec for males and \>470 msec for females, short PR interval (\<120 msec), or PR interval \>220 msec, second- or third-degree 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) \>1.5x ULN or total bilirubin level (TBL) \>1.5x ULN.
* Show evidence of human immunodeficiency virus infection and/or positive human immunodeficiency virus antibodies.
* Show evidence of hepatitis C and/or positive hepatitis C antibody.
* Show evidence of hepatitis B, positive hepatitis B core antibody, and/or positive hepatitis B surface antigen.

Primary outcomes:
measure: Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC [0-∞]) of LY3493269
timeFrame: Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14, 24, 48, 72,120, 288, 624 and 960 hours (h) post-dose
measure: Part A: PK: Area Under the Concentration Versus Time Curve During One Dosing Interval (AUCτ) of LY3493269
timeFrame: Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14 and 24 hours (h) post-dose
measure: Part A: PK: Maximum Observed Drug Concentration (Cmax) of LY3493269
timeFrame: Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14 and 24 hours (h) post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Lilly Centre for Clinical Pharmacology
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: