A First-in-Human Study of LY3009385 in Healthy Participants

A Single Ascending Dose (SAD) Study of LY3009385 in Healthy Volunteers

The main purpose of this study is to determine the safety of LY3009385 in healthy participants. The study drug is given as a single dose, by injections under the skin. Side effects will be documented. This study is approximately 28 days not including screening. Screening is required within 28 days prior to the start of the study.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: LY3009385

Detailed Description

This is a single ascending dose study that examines the safety and tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) effects of single doses of LY3009385 administered subcutaneously to healthy participants. The planned dose levels are 0.3, 1, 3, 9, 27, and 54 milligrams (mg). Within each dose level, participants are randomized to receive either LY3009385 or Placebo.

Adjustments to the dose levels were permitted after review of emerging safety, PK, and glycemic data.

The actual LY3009385 dose levels tested during this study were 0.3, 1, 3, 9, 22, and 54 mg.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Description

Inclusion Criteria:

• Are a healthy male or a female who cannot become pregnant
• Have a body mass index (BMI) of 18.5 to 32.0 kilograms per meter squared (kg/m^2) at screening
• Have blood pressure, pulse rate, as well as blood and urine laboratory test results acceptable for the study
• Have veins suitable for easy blood collection
• Are reliable and willing to be available for the whole study and be willing to follow study procedures
• Have given consent to participate in this study

Exclusion Criteria:

• Are currently participating in or were in another new drug or device or in any medical research study in the last 30 days
• Currently have or used to have allergies or other health problems or laboratory test results that in the opinion of the doctor, could make it unsafe for the participant to participate, or interfere with understanding the results of this study
• Have received live vaccine(s) within 1 month of screening, or intend to during the study
• Have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) prior to dosing
• Have a weakened immune system
• Have previously completed or withdrawn from this study
• Have illnesses or conditions that may increase risk when taking the study medication or interfere with the interpretation of data in this study
• Have electrocardiogram (ECG) readings that are not suitable for the study
• Are using or intend to use over-the-counter medications or prescription medications within 7 and 14 days (respectively) from the start of the first study dosing until end of the study
• Have a history of drug or alcohol abuse
• Are infected with hepatitis B
• Are infected with human immunodeficiency virus (HIV)
• Have donated 450 milliliters (mL) or more of blood in the last 3 months or made any blood donation within the last month
• Have a regular alcohol intake greater than 21 units per week (males) and 14 units per week (females) or are unwilling to abstain from alcohol 24 hours before dosing until the completion of each inpatient study period
• Smoke more than 10 cigarettes per day or are unable or unwilling to refrain from smoking while at the clinic
• Are unwilling or unable to follow dietary requirements/restrictions for the study and only consume only the meals provided during inpatient stays at the clinical research unit
• Are deemed unsuitable to participate by the study doctor for any other reasons

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.3 mg LY3009385; LY3009385: 0.3 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1	Drug: LY3009385
Experimental: 1 mg LY3009385; LY3009385: 1 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1	Drug: LY3009385
Experimental: 3 mg LY3009385; LY3009385: 3 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1	Drug: LY3009385
Experimental: 9 mg LY3009385; LY3009385: 9 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1	Drug: LY3009385
Experimental: 22 mg LY3009385; LY3009385: 22 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1	Drug: LY3009385
Experimental: 54 mg LY3009385; LY3009385: 54 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1	Drug: LY3009385
Placebo Comparator: Placebo; Placebo: saline, subcutaneous (SC) injection, single dose on Day 1	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs	The number of participants with 1 or more AEs assessed as related to the study drug and is summarized cumulatively. In addition, the number of participants with 1 or more serious AEs is summarized cumulatively. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.	Baseline through Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3009385	LY3009385 exposure in terms of AUC from time 0 extrapolated to infinity (AUC[0-inf]) is summarized.	Predose through Day 28
Pharmacokinetics: Maximum Concentration (Cmax)	The maximum observed plasma concentration (Cmax) of LY3009385 is summarized.	Predose through Day 28
Change in Level of Blood Glucose Before and After a Standard Meal	The effect of LY3009385 on postprandial blood glucose was evaluated. Change from baseline area under the glucose concentration-time curve from time 0 to 6 hours after participants started eating a standardized breakfast (mixed-meal tolerance test) was calculated and summarized by treatment arm.	Baseline, Day 5, and Day 14
Change in Level of C-peptide Before and After a Standard Meal	The effect of LY3009385 on postprandial c-peptide was assessed. Change from baseline area under the c-peptide concentration-time curve from time 0 to 4 hours after participants started eating a standardized breakfast (mixed-meal tolerance test) was calculated and summarized by treatment arm.	Baseline, Day 5, and Day 14
Change in Level of Glucagon Before and After a Standard Meal	The effect of LY3009385 on postprandial glucagon levels was assessed. Change from baseline glucagon concentrations 2 hours after participants started eating a standardized breakfast (mixed-meal tolerance test) were calculated and summarized by treatment arm.	Baseline, Day 14
Number of Participants Forming Antibody to LY3009385	The number of participants with postbaseline detection of LY3009385treatment-emergent (TE) antidrug antibodies (ADA), defined as a 4-fold increase in the ADA titer from baseline.	Baseline through Day 28

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: November 18, 2011
• First Submitted That Met QC Criteria: November 18, 2011
• First Posted (Estimate): November 22, 2011

Study Record Updates

• Last Update Posted (Estimate): October 6, 2014
• Last Update Submitted That Met QC Criteria: October 2, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 14195; I5O-FW-GTCA (Other Identifier: Eli Lilly and Company)