A Study of LY3143753 and LY3185643 in Healthy Participants

A Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3143753 and LY3185643 in Healthy Subjects

The study involves a single dose of LY3143753 or LY3185643, given as an injection into the abdomen. The study will evaluate the effects of the LY3143753 or LY3185643 on your body. The study is approximately 12 weeks for each participant, not including screening. Screening is required within 28 days prior to the start of the study. This study involves Part A (LY3143753) and Part B (LY3185643). Participants may only enroll in one part and at one dose level.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LY3143753 (Part A); Drug: LY3185643 (Part B); Drug: Placebo (Part A and Part B); Drug: rGlucagon (Part B)

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Overtly healthy males or females
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

Exclusion Criteria:

• Are investigator site personnel directly affiliated with this study and their immediate families
• Are currently enrolled in a clinical trial involving an investigational product (IP) or off-label use of a drug or device
• Have participated, within the last 3 months, in a clinical trial
• Have known or ongoing psychiatric disorders
• Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
• Show evidence of hepatitis C and/or positive hepatitis C antibody
• Show evidence of hepatitis B and/or positive hepatitis B surface antigen
• History of/current phaeochromocytoma
• History of/current insulinoma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3143753 (Part A); Single subcutaneous (SC) injection of ascending doses of LY3143753 on Day 1	Drug: LY3143753 (Part A); Administered via SC injection
Experimental: LY3185643 (Part B); Single SC injection of ascending doses of LY3185643 on Day 1	Drug: LY3185643 (Part B); Administered via SC injection
Placebo Comparator: Placebo (Part A); Single SC injection of normal saline on Day 1	Drug: Placebo (Part A and Part B); Administered via SC injection
Active Comparator: rGlucagon (Part B); Single SC injection on Day 1	Drug: rGlucagon (Part B); Administered via SC injection
Placebo Comparator: Placebo (Part B); Single SC injection of normal saline on Day 1	Drug: Placebo (Part A and Part B); Administered via SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.	Baseline to Study Completion (Up to 84 Days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
PK: Cmax of Part B	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
PK: AUC(0-∞) of Part B	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
PK: Time to Maximum Drug Concentration (Tmax) of Part A	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
PK: Tmax of Part B	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
PD Absolute Maximum Blood Glucose of Part B	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
PD: Maximum Glucose Increase (Gmax) of Part A	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
PD: Gmax of Part B	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
PD: Time to Maximum Blood Glucose (Gtmax) of Part A	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
PD: Gtmax of Part B	Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A	Baseline, 8 hours after drug administration
QTcF Change From Baseline of Part B	Baseline, 8 hours after drug administration

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: January 14, 2015
• First Submitted That Met QC Criteria: January 14, 2015
• First Posted (Estimate): January 19, 2015

Study Record Updates

• Last Update Posted (Actual): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 15503; I7U-MC-GAHA (Other Identifier: Eli Lilly and Company)