Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to evaluate the effect on the electrical activity of the heart as measured by an electrocardiogram (ECG) after dosing with 10 days of LY2484595 compared to 10 days of placebo in relation to a single dose of moxifloxacin. Information about any side effects that occur will also be collected.
Interventions
DRUGLY2484595
Administered orally once daily for 10 days.
DRUGPlacebo
Administered orally once daily for 10 days.
DRUGMoxifloxacin
Single dose administered orally.
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
* Healthy males and females * Body mass index (BMI) of 18.5 to 29 kilograms per square meter (kg/m²) * Reliable and willing to be available for the duration of the study and are willing to follow study procedures * Provided written informed consent
Exclusion criteria
* Known allergies to LY2484595 or moxifloxacin * Personal or family history of long QT syndrome, heart failure, or low blood potassium (hypokalemia) a family history of sudden death, or unexplained syncope within the last year * Positive findings on urinary drug screening * Cigarette smokers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo | Predose of Day 1, Day 10 | Data were collected using a 12-lead electrocardiogram (ECG). The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle and corrected for heart rate. Population-corrected QT interval (QTcP) formula: QTcP = QT / RR\^ß, where ß is the population correction factor. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2484595 During One Dosing Interval at Steady State | Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours Postdose |
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2484595 During One Dosing Interval at Steady State | Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours Postdose |
| Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | Baseline, Day 11 |
Countries
United States
Participant flow
Pre-assignment details
Participants were randomized to 1 of 6 treatment sequences in a crossover design with 3 treatments; 1200 mg LY2484595, then placebo, then moxifloxacin. There was a washout period of ≥14 days between each dose. Participants were dosed 3 times during the entire study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Placebo or 1200 mg LY2484595 administered orally once daily for 10 days, or 400 mg moxifloxacin single oral dose on Day 1 during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods. | 71 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Did not receive treatment | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 1 | Physician Decision | 0 | 0 | 0 | 0 | 1 | 1 |
| Period 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
| Period 3 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 3 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 43.1 years STANDARD_DEVIATION 13.3 |
| Race/Ethnicity, Customized Black or African American | 17 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants |
| Race/Ethnicity, Customized White | 53 Participants |
| Region of Enrollment United States | 71 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 70 | 24 / 69 | 11 / 69 |
| serious Total, serious adverse events | 0 / 70 | 1 / 69 | 0 / 69 |
Outcome results
Primary
Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo
Data were collected using a 12-lead electrocardiogram (ECG). The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle and corrected for heart rate. Population-corrected QT interval (QTcP) formula: QTcP = QT / RR\^ß, where ß is the population correction factor.
Time frame: Predose of Day 1, Day 10
Population: All participants who received at least one dose of study drug and had both baseline and post-baseline ECG measurements on Day 10.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo | 4-hour postdose on Day 10 | -2.7 milliseconds (msec) | Standard Deviation 7.5 |
| Placebo | Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo | 6-hour postdose on Day 10 | -2.0 milliseconds (msec) | Standard Deviation 7.7 |
| LY2484595 | Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo | 4-hour postdose on Day 10 | -4.6 milliseconds (msec) | Standard Deviation 8.5 |
| LY2484595 | Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo | 6-hour postdose on Day 10 | -1.1 milliseconds (msec) | Standard Deviation 8.5 |
Secondary
Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins
Time frame: Baseline, Day 11
Population: All participants who received at least one dose of study drug and had both baseline and post-baseline lipid or apolipoprotein (Apo) measurements on Day 11.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | High-density lipoprotein cholesterol (HDL-C) | -8 percentage change | Standard Deviation 15 |
| Placebo | Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | Low-density lipoprotein cholesterol (LDL-C) | 9 percentage change | Standard Deviation 17 |
| Placebo | Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | Apo-A1 | -9 percentage change | Standard Deviation 13 |
| Placebo | Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | Apo-B | 8 percentage change | Standard Deviation 16 |
| LY2484595 | Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | Apo-B | -24 percentage change | Standard Deviation 18 |
| LY2484595 | Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | High-density lipoprotein cholesterol (HDL-C) | 112 percentage change | Standard Deviation 37 |
| LY2484595 | Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | Apo-A1 | 32 percentage change | Standard Deviation 18 |
| LY2484595 | Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins | Low-density lipoprotein cholesterol (LDL-C) | -35 percentage change | Standard Deviation 16 |
Secondary
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2484595 During One Dosing Interval at Steady State
Time frame: Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours Postdose
Population: Participants who received at least one dose of LY2484595 and had pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2484595 During One Dosing Interval at Steady State | 48300 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 49 |
Secondary
Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2484595 During One Dosing Interval at Steady State
Time frame: Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours Postdose
Population: Participants who received at least one dose of LY2484595 and had pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2484595 During One Dosing Interval at Steady State | 5270 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 65 |