Diabetes Mellitus, Type 2
Conditions
Brief summary
Part A: The purpose of Part A of the study is to look at the electrocardiogram (ECG) effects due to blood sugar changes after a meal compared to when LY2409021 is also given with a meal. Part B: The purpose of Part B is to evaluate the effect of LY2409021, when given at a dose level much higher than what would normally be given, on the electrical activity of the heart as measured by ECG in relation to placebo and moxifloxacin.
Detailed description
This is a 2 part study. Part A is a single-dose study to compare the effects of a meal on glucose, insulin and QT in healthy participants with and without LY2409021. Part B of this study is a randomized, 3-period, crossover design, in which participants and investigators are blinded to placebo and LY2409021, and will assess the electrophysiological effects of a single supratherapeutic dose of LY2409021 compared to a positive control (moxifloxacin) and placebo.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* are overtly healthy males or females, as determined by medical history and physical examination * female participants: women not of child-bearing potential due to surgical sterilization (hysterectomy alone or at least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history, or menopause Women with an intact uterus are deemed postmenopausal if they are \>=45 years old, have not taken hormones or oral contraceptives within the last year, had cessation of menses for at least 1 year, or have had 6 to 12 months of amenorrhea with follicle-stimulating hormone levels consistent with postmenopausal state * have a body mass index (BMI) of 18.5 to 32 kilograms per meter squared (kg/m\^2), inclusive, at screening * have a fasting blood glucose between 54 to 110 milligrams per deciliter (mg/dL) (3.0 to 6.1 millimoles per liter \[mmol/L\]) * have a clinically normal screening electrocardiogram (ECG) with a measurable QT interval as judged by central reader, which allows accurate measurements of QT interval * have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator * have venous access sufficient to allow for blood sampling * are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * have normal blood pressure and pulse rate (supine) at screening, or with minor deviations judged to be acceptable by the investigator * have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site * serum magnesium and potassium equal to or above the lower limit of normal
Exclusion criteria
* are currently enrolled in or have completed or discontinued within the last 30 days (from screening) from a clinical trial involving an investigational product; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * have known allergies to LY2409021, related compounds or any components of the formulations, or to moxifloxacin * are persons who have previously received the investigational product in this study, have completed or withdrawn from this study or any other study investigating LY2409021 * personal or family history of long QT syndrome * family history of sudden unexplained death or cardiac death in a family member under 60 years of age * personal history of unexplained syncope within the last year * have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data * regularly use known drugs of abuse and/or show positive findings on urinary drug screening * 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 * are women with a positive pregnancy test or women who are lactating * intend to use over-the-counter (including mineral supplements and herbal medicine) or prescription medication within 7 days prior to dosing * have donated blood of more than 500 milliliters (mL) within the last month * have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) (1 unit = 12 ounces \[oz\] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits), or are unwilling to comply with alcohol restrictions during the study (that is, refrain from alcohol consumption from 24 hours prior to dosing until the completion of each treatment period and to consume no more than 2 units of alcohol per day between treatment periods) * are participants who smoke more than 10 cigarettes per day and/or are unable to abide by the study restrictions for smoking/tobacco use (that is, refrain from smoking for approximately 2 hours prior to each ECG timepoint or for a total of approximately 12 hours) * are participants who are unable to abide by the study restrictions for caffeine/xanthine use (that is, refrain from consuming caffeine/xanthine containing drinks and foods \[such as coffee, tea, cola, and chocolate\] on days on which ECGs are performed, and maintain consistent consumption habits on all other days of the study)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | Baseline, 2, 4, 6, 8, 12, and 24 hours | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Least Squares (LS) means were calculated using mixed effects model with fixed effects for treatment, time, period, sequence, and the time-by-treatment interaction, random effects for participant, the participant-by-treatment interaction, and participant-by-time interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin) | Baseline, 2 and 4 hours | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Least Squares (LS) means were calculated using mixed effects model with fixed effects for treatment, time, period, sequence, and the time-by-treatment interaction, random effects for participant, the participant-by-treatment interaction, and participant-by-time interaction. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A A single dose of 300 milligrams (mg) LY2409021 administered orally on Day 1. Participants enrolled in Part A were not allowed to participate in Part B. | 7 |
| Part B Participants received a single dose of either 300 milligrams (mg) LY2409021, 400 mg Moxifloxacin, or Placebo on Day 1 in 1 of 3 Study Periods so that after the completion of the 3 study periods, each participant received a single dose of each drug. | 60 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Part B: First Intervention (Period 1) | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part B: Second Intervention (Period 2) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part B: Second Intervention (Period 2) | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Part B: Third Interventions (Period 3) | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 1 | 0 |
| Part B: Washout (up to 15 Days) | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A | Total | Part B |
|---|---|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 7.7 | 40.4 years STANDARD_DEVIATION 12.5 | 39.7 years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 23 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 44 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 26 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 39 Participants | 35 Participants |
| Region of Enrollment United States | 7 Participants | 67 Participants | 60 Participants |
| Sex: Female, Male Female | 0 Participants | 14 Participants | 14 Participants |
| Sex: Female, Male Male | 7 Participants | 53 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 7 | 12 / 57 | 11 / 58 | 9 / 59 |
| serious Total, serious adverse events | 0 / 7 | 0 / 57 | 0 / 58 | 0 / 59 |
Outcome results
Primary
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Least Squares (LS) means were calculated using mixed effects model with fixed effects for treatment, time, period, sequence, and the time-by-treatment interaction, random effects for participant, the participant-by-treatment interaction, and participant-by-time interaction.
Time frame: Baseline, 2, 4, 6, 8, 12, and 24 hours
Population: Participants who received at least 1 dose of LY2409021 or Placebo with evaluable Fridericia Correction Formula (QTcF) data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part B: LY2409021 | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 2 hours postdose | -14.72 milliseconds |
| Part B: LY2409021 | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 4 hours postdose | -5.43 milliseconds |
| Part B: LY2409021 | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 6 hours postdose | 6.13 milliseconds |
| Part B: LY2409021 | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 8 hours postdose | 7.80 milliseconds |
| Part B: LY2409021 | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 12 hours postdose | -13.45 milliseconds |
| Part B: LY2409021 | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 24 hours postdose | -1.32 milliseconds |
| Part B: Placebo | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 12 hours postdose | -13.30 milliseconds |
| Part B: Placebo | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 2 hours postdose | -15.35 milliseconds |
| Part B: Placebo | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 8 hours postdose | -1.29 milliseconds |
| Part B: Placebo | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 4 hours postdose | -9.12 milliseconds |
| Part B: Placebo | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 24 hours postdose | -4.95 milliseconds |
| Part B: Placebo | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) | 6 hours postdose | -3.01 milliseconds |
90% CI: [-1.38, 2.63]
90% CI: [1.67, 5.71]
90% CI: [7.12, 11.16]
90% CI: [7.1, 11.07]
90% CI: [-2.14, 1.85]
90% CI: [1.63, 5.63]
Secondary
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin)
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Least Squares (LS) means were calculated using mixed effects model with fixed effects for treatment, time, period, sequence, and the time-by-treatment interaction, random effects for participant, the participant-by-treatment interaction, and participant-by-time interaction.
Time frame: Baseline, 2 and 4 hours
Population: Participants who received at least 1 dose of Moxifloxacin or Placebo with evaluable QTcF data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part B: LY2409021 | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin) | 2 hours postdose | -7.39 milliseconds |
| Part B: LY2409021 | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin) | 4 hours postdose | 1.45 milliseconds |
| Part B: Placebo | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin) | 2 hours postdose | -15.46 milliseconds |
| Part B: Placebo | Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin) | 4 hours postdose | -9.11 milliseconds |
90% CI: [5.21, 10.94]
90% CI: [7.69, 13.43]