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

Phase 1
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Drug: Placebo
Registration Number
NCT01477567
Lead Sponsor
Eli Lilly and Company
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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  • Have previously completed or withdrawn from this study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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
54 mg LY3009385LY3009385LY3009385: 54 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1
9 mg LY3009385LY3009385LY3009385: 9 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1
0.3 mg LY3009385LY3009385LY3009385: 0.3 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1
22 mg LY3009385LY3009385LY3009385: 22 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1
1 mg LY3009385LY3009385LY3009385: 1 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1
3 mg LY3009385LY3009385LY3009385: 3 milligrams (mg), subcutaneous (SC) injection, single dose on Day 1
PlaceboPlaceboPlacebo: saline, subcutaneous (SC) injection, single dose on Day 1
Primary Outcome Measures
NameTimeMethod
Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEsBaseline through Day 28

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.

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3009385Predose through Day 28

LY3009385 exposure in terms of AUC from time 0 extrapolated to infinity (AUC\[0-inf\]) is summarized.

Pharmacokinetics: Maximum Concentration (Cmax)Predose through Day 28

The maximum observed plasma concentration (Cmax) of LY3009385 is summarized.

Change in Level of Blood Glucose Before and After a Standard MealBaseline, Day 5, and Day 14

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.

Change in Level of C-peptide Before and After a Standard MealBaseline, Day 5, and Day 14

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.

Change in Level of Glucagon Before and After a Standard MealBaseline, Day 14

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.

Number of Participants Forming Antibody to LY3009385Baseline through Day 28

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.

Trial Locations

Locations (1)

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.

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