The Effects of LY2409021 on the Liver

Effects of LY2409021 on Hepatic Metabolism in Healthy Volunteers and Patients With Type 2 Diabetes Mellitus

This is a study that involves multiple doses of study drug (60 mg of LY2409021, 15 mg of LY2409021 or placebo) taken as capsules by mouth on a daily basis for 28 days. This study will image the liver using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in healthy participants and in participants with type 2 diabetes mellitus, when they take LY2409021 to see if liver changes happen at the same time as changes in blood tests. This study is approximately 11 weeks long, not including screening. A screening appointment 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: LY2409021

• Study Type: Interventional
• Enrollment (Actual): 30
• 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 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For all participants:

• Must be a male, or a female who cannot become pregnant, and who is either a healthy participant, or who has type 2 diabetes
• Must have a body mass index (BMI) of 18.5 to 29.9 kilograms per square meter (kg/m^2) if a healthy participant, or a BMI of 18.5 to 35.0 kg/m^2 if diabetic

For participants with type 2 diabetes mellitus (T2DM):

- On diet and exercise treatment, or taking metformin

Exclusion Criteria:

For all participants:

• Have signs or symptoms of liver disease
• Are infected with hepatitis B or hepatitis C
• Have donated more than 450 mL of blood in the last 3 months or if have donated any blood in the last month
• Smoke more than 10 cigarettes per day or are not willing to abstain from smoking while at the clinic
• Have had surgery with metallic clips, staples or stents, or have had a cardiac pacemaker (or other surgical implants) inserted in any part of the body, or have fear of enclosed spaces or have symptoms that prevent them from being sent for an magnetic resonance imaging (MRI) scan

For participants with T2DM:

- Are using insulin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Part A and B - Up to 4 capsules of placebo administered orally once a day for 28 days.	Drug: Placebo; Administered orally
Experimental: 15 mg LY2409021; Part B - 1 capsule of 15 mg LY2409021 orally once a day for 28 days. (Arm added in September, 2012, per protocol amendment.)	Drug: LY2409021; Administered orally
Experimental: 60 mg LY2409021; Part A - 4 capsules of 15 mg LY2409021 administered orally once a day for 28 days.	Drug: LY2409021; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 28 in Liver Fat Average Percent (%)	Measured by magnetic resonance (MR) scanning.	Baseline, Day 28 (Pre-meal)
Change From Baseline to Day 28 in Hepatic Glycogen Content	Measured by MR scanning.	Baseline, Day 28 (Pre-meal)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 28 in Transaminase Levels		Baseline, Day 28
Change From Baseline to Day 29 in Glucose Response to an Arginine Stimulation Test (AST) (Part A)	Acute glucose response to an AST at a blood glucose level of approximately 250 milligrams per deciliter (mg/dL).	Baseline, Day 29
Change From Baseline to Day 29 in Glucagon Response to an Arginine Stimulation Test (AST) (Part A)	Acute glucagon response to an AST at a blood glucose level of approximately 250 mg/dL.	Baseline, Day 29
Change From Baseline to Day 29 in Insulin Response to an Arginine Stimulation Test (AST) (Part A)	Acute insulin response to an AST at a blood glucose level of approximately 250 mg/dL.	Baseline, Day 29

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: April 27, 2012
• First Posted (Estimate): May 1, 2012

Study Record Updates

• Last Update Posted (Actual): March 7, 2019
• Last Update Submitted That Met QC Criteria: November 16, 2018
• Last Verified: November 1, 2018

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: 13107; I1R-FW-GLBK (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

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