A Study of LY3451838 in Healthy Participants

A Safety, Tolerability, and Pharmacokinetics Study of LY3451838 in Healthy Subjects

The study has two parts. In Part A, single increasing doses of LY3451838 will be administered intravenously (into a vein). In Part B, a single dose of LY3451838 will be administered subcutaneously (just under the skin).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LY3451838; Drug: LY3451838; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 138623
    • Lilly Centre for Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male participants must adhere to contraception restrictions

• Female participants must be of non-childbearing potential due to:

  • Menopause: spontaneous amenorrhea for at least 12 months not induced by a medical condition such as anorexia nervosa and not taking medications that induced the amenorrhea (e.g., oral contraceptives, hormones, gonadotropin releasing hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy)
  • Surgical sterilization
• Have a body mass index of 18 to 35 kilograms per square meter (kg/m²)
• Have clinical laboratory test results within normal reference range or with acceptable deviations
• Have an estimated glomerular filtration rate greater than or equal to (≥) 60 milliliters per minute per 1.73 meters squared (mL/minute/1.73 m²) of body surface area
• Have venous access sufficient to allow for blood sampling

Exclusion Criteria:

• Are currently enrolled in or discontinued from a clinical trial within the last 30 days, or have previously completed or withdrawn from this study
• Have a history or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, renal, endocrine, psychiatric or neurological disease, or any clinically significant laboratory abnormality
• Have history of or presence of uncontrolled asthma, significant atopy, or significant rheumatological or autoimmune diseases
• Have had lymphoma, leukemia, or any malignancy within the past 5 years, or breast cancer within the past 10 years (with some exceptions)
• Have used, or intend to use some prescription or over the counter medications, including herbal medications within 14 days prior to dosing
• Have an abnormality in the 12-lead electrocardiogram (ECG) or Fridericia's corrected QT (QTcF)
• Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies, hepatitis C and/or positive hepatitis C antibody, or hepatitis B and/or positive hepatitis B surface antigen
• Have donated blood of more than 450 milliliters (mL) within the last 3 months
• Are unwilling to stop alcohol consumption while resident in the Clinical Research Unit (CRU)
• Have an average weekly alcohol intake that exceeds 21 units per week for males and 14 units per week for females (1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
• Current smoker of more than 10 cigarettes or equivalent per day and unable to stop smoking while in the CRU
• Have an abnormal blood pressure
• Have clinically significant proteinuria or hematuria
• Positive findings for known drugs of abuse
• Have received treatment with biologic agents within 3 months or 5 half-lives (whichever is longer)
• Have clinically significant allergies, or intolerance to corticosteroids, or severe post treatment hypersensitivity reactions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 25 milligram (mg) LY3451838 Part A; 25 mg LY3451838 single dose administered intravenously (IV)	Drug: LY3451838; Administered IV Part A; Drug: LY3451838; Administered SC Part B
Experimental: 75 mg LY3451838 Part A; 75 mg LY3451838 single dose administered IV.	Drug: LY3451838; Administered IV Part A; Drug: LY3451838; Administered SC Part B
Experimental: 250 mg LY3451838 Part A; 250 mg LY3451838 single dose administered IV.	Drug: LY3451838; Administered IV Part A; Drug: LY3451838; Administered SC Part B
Experimental: 500 mg LY3451838 Part A; 500 mg LY3451838 single dose administered IV.	Drug: LY3451838; Administered IV Part A; Drug: LY3451838; Administered SC Part B
Experimental: 1000 mg LY3451838 Part A; 1000 mg LY3451838 single dose administered IV.	Drug: LY3451838; Administered IV Part A; Drug: LY3451838; Administered SC Part B
Experimental: 1500 mg LY3451838 Part A; 1500 mg LY3451838 single dose administered IV.	Drug: LY3451838; Administered IV Part A; Drug: LY3451838; Administered SC Part B
Experimental: 250 mg LY3451838 Part B; 250 mg LY3451838 single dose administered subcutaneously (SC).	Drug: LY3451838; Administered IV Part A; Drug: LY3451838; Administered SC Part B
Placebo Comparator: Placebo; Placebo matching single dose administered IV in Part A or administered SC in Part B.	Drug: Placebo; Administered IV in Part A and SC in Part B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Treatment Emergent Adverse Event	A summary of other non-serious Adverse Events (AE's), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.	Baseline through 20 Weeks
Number of Participants With One or More Serious Adverse Events	A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.	Baseline through 20 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838	PK: AUC of LY3451838	Part A: Predose, End of Infusion, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose; Part B: Predose, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838	PK: Cmax of LY3451838	Part A: Predose, End of Infusion, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose; Part B: Predose, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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

Publications and helpful links

General Publications

• Johnson MP, Krikke-Workel J, Patel CN, Morin SM, Turner PK, Clark KA, Donley D, Jin Y, Johnson KW, Vincent M, Stille JR, Broad LM, Patel A. Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine. Cephalalgia. 2025 Aug;45(8):3331024251368757. doi: 10.1177/03331024251368757. Epub 2025 Aug 21.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2018
• Primary Completion (Actual): February 26, 2020
• Study Completion (Actual): February 26, 2020

Study Registration Dates

• First Submitted: October 1, 2018
• First Submitted That Met QC Criteria: October 1, 2018
• First Posted (Actual): October 2, 2018

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 17123; J1H-MC-LAJA (Other Identifier: Eli Lilly & Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No