A Multiple-Dose Study of LY3493269 in Healthy Participants

NCT05794243 | Terminated Phase 1 Results

• 2 other identifiers: 18360J1X-MC-GZHI
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC [0-∞]) of LY3493269

  PK: AUC (0-∞) of LY3493269

  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

• Part A: PK: Area Under the Concentration Versus Time Curve During One Dosing Interval (AUCτ) of LY3493269

  PK: AUCτ of LY3493269

  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

• Part A: PK: Maximum Observed Drug Concentration (Cmax) of LY3493269

  Cmax of LY3493269

  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

Study Arms (4)

Part A: 4 mg LY3493269 Test Capsule 1 + 280 mg C10 (Fasted)

EXPERIMENTAL

* Participants were administered oral doses of 4 milligram (mg) LY3493269 test capsule formulation 1, co-administered with 280 mg of sodium caprate (C10). * This regimen was administered once daily on Days 1, 2, and 3, following an overnight fast.

Drug: LY3493269; Drug: Sodium Caprate (C10)

Part A: 4 mg LY3493269 Test Capsule 2 + 280 mg C10 (Fasted)

EXPERIMENTAL

* Participants were administered oral doses of 4 mg LY3493269 test capsule formulation 2, co-administered with 280 mg of C10. * This regimen was administered once daily on Days 1, 2, and 3, following an overnight fast.

Drug: LY3493269; Drug: Sodium Caprate (C10)

Part A: 4 mg LY3493269 Reference Tablet + 300 mg SNAC (Fasted)

EXPERIMENTAL

* Participants were administered oral doses of 4 mg LY3493269 reference tablet formulation, co-administered with 300 mg of salcaprozate sodium (SNAC). * This regimen was administered once daily on Days 1, 2, and 3, following an overnight fast.

Drug: LY3493269; Drug: Salcaprozate Sodium (SNAC)

Part B: LY3493269

EXPERIMENTAL

The formulation of the LY3493269 test capsule (1,2) or reference tablet were planned to be determined based on the initial review of safety and pharmacokinetic data from Part A.

Drug: LY3493269

Interventions

LY3493269 DRUG

Administered orally.

Part A: 4 mg LY3493269 Reference Tablet + 300 mg SNAC (Fasted); Part A: 4 mg LY3493269 Test Capsule 1 + 280 mg C10 (Fasted); Part A: 4 mg LY3493269 Test Capsule 2 + 280 mg C10 (Fasted); Part B: LY3493269

Sodium Caprate (C10) DRUG

Administered orally.

Part A: 4 mg LY3493269 Test Capsule 1 + 280 mg C10 (Fasted); Part A: 4 mg LY3493269 Test Capsule 2 + 280 mg C10 (Fasted)

Salcaprozate Sodium (SNAC) DRUG

Administered orally.

Part A: 4 mg LY3493269 Reference Tablet + 300 mg SNAC (Fasted)

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Lilly Centre for Clinical Pharmacology

Singapore, 138623, Singapore

Location

MeSH Terms

Interventions

decanoic acid; Neprilysin; N-(8-(2-hydroxybenzoyl)amino)caprylate

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Antigens, Neoplasm; Antigens; Biological Factors; Biomarkers, Tumor; Biomarkers

Limitations and Caveats

The study was terminated early, and Part B was not executed, as sufficient safety and pharmacokinetic data had already been obtained from Part A.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 3, 2023
• Study Start: March 23, 2023
• Primary Completion: June 20, 2023
• Study Completion: June 20, 2023
• Last Updated: January 14, 2025
• Results First Posted: January 14, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)