Diabetes Mellitus, Type 2
Conditions
Brief summary
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.
Interventions
DRUGPlacebo
Administered orally
DRUGLY2409021
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 28 in Liver Fat Average Percent (%) | Baseline, Day 28 (Pre-meal) | Measured by magnetic resonance (MR) scanning. |
| Change From Baseline to Day 28 in Hepatic Glycogen Content | Baseline, Day 28 (Pre-meal) | Measured by MR scanning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Baseline, Day 29 | Acute glucose response to an AST at a blood glucose level of approximately 250 milligrams per deciliter (mg/dL). |
| Change From Baseline to Day 29 in Glucagon Response to an Arginine Stimulation Test (AST) (Part A) | Baseline, Day 29 | Acute glucagon response to an AST at a blood glucose level of approximately 250 mg/dL. |
| Change From Baseline to Day 29 in Insulin Response to an Arginine Stimulation Test (AST) (Part A) | Baseline, Day 29 | Acute insulin response to an AST at a blood glucose level of approximately 250 mg/dL. |
Countries
Singapore
Participant flow
Recruitment details
Study started in April, 2012 with Part A. Part B was added per protocol amendment in September, 2012.
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Healthy (Part A) Placebo administered orally, QD for 28 days to healthy participants. | 2 |
| 60 mg LY2409021 - Healthy (Part A) 60 mg LY2409021 administered orally, QD for 28 days to healthy participants. | 7 |
| Placebo - T2DM (Parts A and B) Placebo administered orally, QD for 28 days to participants with T2DM. | 5 |
| 15 mg LY2409021 - T2DM (Part B) 15 mg LY2409021 administered orally, QD for 28 days to participants with T2DM. | 9 |
| 60 mg LY2409021 - T2DM (Part A) 60 mg LY2409021 administered orally, QD for 28 days to participants with T2DM. | 7 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo - Healthy (Part A) | 60 mg LY2409021 - Healthy (Part A) | Placebo - T2DM (Parts A and B) | 15 mg LY2409021 - T2DM (Part B) | 60 mg LY2409021 - T2DM (Part A) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous Healthy Participants | 49.5 years STANDARD_DEVIATION 13.4 | 39.3 years STANDARD_DEVIATION 13.2 | NA years | NA years | NA years | 41.6 years STANDARD_DEVIATION 13.2 |
| Age, Continuous T2DM subjects | NA years | NA years | 60.0 years STANDARD_DEVIATION 5.1 | 55.7 years STANDARD_DEVIATION 7.9 | 51.4 years STANDARD_DEVIATION 10 | 55.3 years STANDARD_DEVIATION 8.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 5 Participants | 9 Participants | 7 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Singapore | 2 Participants | 7 Participants | 5 Participants | 9 Participants | 7 Participants | 30 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 4 Participants | 8 Participants | 5 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 2 | 7 / 7 | 4 / 5 | 7 / 9 | 4 / 7 |
| serious Total, serious adverse events | 0 / 2 | 0 / 7 | 0 / 5 | 2 / 9 | 0 / 7 |
Outcome results
Primary
Change From Baseline to Day 28 in Hepatic Glycogen Content
Measured by MR scanning.
Time frame: Baseline, Day 28 (Pre-meal)
Population: All participants in Part A who received 60 mg LY2409021 and had evaluable MR scans at Baseline and on Day 28.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo - Healthy (Part A) | Change From Baseline to Day 28 in Hepatic Glycogen Content | 12.8 millimoles per liter (mmol/L) |
| 60 mg LY2409021 - Healthy (Part A) | Change From Baseline to Day 28 in Hepatic Glycogen Content | 42.1 millimoles per liter (mmol/L) |
Primary
Change From Baseline to Day 28 in Liver Fat Average Percent (%)
Measured by magnetic resonance (MR) scanning.
Time frame: Baseline, Day 28 (Pre-meal)
Population: All participants who had evaluable MR scans at Baseline and on Day 28.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo - Healthy (Part A) | Change From Baseline to Day 28 in Liver Fat Average Percent (%) | -0.47 percentage of liver fat average |
| 60 mg LY2409021 - Healthy (Part A) | Change From Baseline to Day 28 in Liver Fat Average Percent (%) | 5.55 percentage of liver fat average |
| Placebo - T2DM (Parts A and B) | Change From Baseline to Day 28 in Liver Fat Average Percent (%) | -1.49 percentage of liver fat average |
| 15 mg LY2409021 - T2DM (Part B) | Change From Baseline to Day 28 in Liver Fat Average Percent (%) | 4.45 percentage of liver fat average |
| 60 mg LY2409021 - T2DM (Part A) | Change From Baseline to Day 28 in Liver Fat Average Percent (%) | 5.84 percentage of liver fat average |
Secondary
Change From Baseline to Day 28 in Transaminase Levels
Time frame: Baseline, Day 28
Population: All participants who had evaluable transaminase levels at Baseline and on Day 28.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - Healthy (Part A) | Change From Baseline to Day 28 in Transaminase Levels | Alanine aminotransferase (ALT) | -0.5 units per liter (U/L) | Standard Deviation 0.7 |
| Placebo - Healthy (Part A) | Change From Baseline to Day 28 in Transaminase Levels | Aspartate aminotransferase (AST) | 0.3 units per liter (U/L) | Standard Deviation 3.2 |
| 60 mg LY2409021 - Healthy (Part A) | Change From Baseline to Day 28 in Transaminase Levels | Alanine aminotransferase (ALT) | 47.7 units per liter (U/L) | Standard Deviation 51.6 |
| 60 mg LY2409021 - Healthy (Part A) | Change From Baseline to Day 28 in Transaminase Levels | Aspartate aminotransferase (AST) | 22.2 units per liter (U/L) | Standard Deviation 22.8 |
| Placebo - T2DM (Parts A and B) | Change From Baseline to Day 28 in Transaminase Levels | Alanine aminotransferase (ALT) | -3.5 units per liter (U/L) | Standard Deviation 4.3 |
| Placebo - T2DM (Parts A and B) | Change From Baseline to Day 28 in Transaminase Levels | Aspartate aminotransferase (AST) | -0.2 units per liter (U/L) | Standard Deviation 3.7 |
| 15 mg LY2409021 - T2DM (Part B) | Change From Baseline to Day 28 in Transaminase Levels | Aspartate aminotransferase (AST) | 9.9 units per liter (U/L) | Standard Deviation 9.5 |
| 15 mg LY2409021 - T2DM (Part B) | Change From Baseline to Day 28 in Transaminase Levels | Alanine aminotransferase (ALT) | 15.7 units per liter (U/L) | Standard Deviation 15.1 |
| 60 mg LY2409021 - T2DM (Part A) | Change From Baseline to Day 28 in Transaminase Levels | Alanine aminotransferase (ALT) | 13.3 units per liter (U/L) | Standard Deviation 5.8 |
| 60 mg LY2409021 - T2DM (Part A) | Change From Baseline to Day 28 in Transaminase Levels | Aspartate aminotransferase (AST) | 7.7 units per liter (U/L) | Standard Deviation 4.8 |
Secondary
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.
Time frame: Baseline, Day 29
Population: All participants in Part A who received 60 mg LY2409021 and had an evaluable glucagon response at Baseline and on Day 29.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo - Healthy (Part A) | Change From Baseline to Day 29 in Glucagon Response to an Arginine Stimulation Test (AST) (Part A) | 80.0 pmol/L |
| 60 mg LY2409021 - Healthy (Part A) | Change From Baseline to Day 29 in Glucagon Response to an Arginine Stimulation Test (AST) (Part A) | 103 pmol/L |
Secondary
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).
Time frame: Baseline, Day 29
Population: Zero participants were analyzed for this outcome measure because glucose response data was not collected or included in the data analysis plan.
Secondary
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.
Time frame: Baseline, Day 29
Population: All participants in Part A who received 60 mg LY2409021 and had an evaluable insulin response at Baseline and on Day 29.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo - Healthy (Part A) | Change From Baseline to Day 29 in Insulin Response to an Arginine Stimulation Test (AST) (Part A) | -34.7 pmol/L |
| 60 mg LY2409021 - Healthy (Part A) | Change From Baseline to Day 29 in Insulin Response to an Arginine Stimulation Test (AST) (Part A) | 139 pmol/L |