Healthy Participants
Conditions
Brief summary
This is a single-centre, placebo-controlled, two-part study in healthy participants. Part A will be a single dose, single period, placebo-controlled pilot study to explore the safety, tolerability, absorption and pharmacodynamic \[effect of drug on a biological marker-phospho-S6 (pS6) levels in skin biopsies\] of a single dose of 25 milligrams (mg) LY2584702 Reference formulation (RF). Part B is a single dose, placebo-controlled, 4-period crossover study to primarily evaluate the absorption of the Test Formulation (TF) in comparison with the (RF) of LY2584702.
Interventions
DRUGLY2584702 Reference Formulation
Administered orally
DRUGLY2584702 Test Formulation
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Male participants: • Agree to use a reliable method of birth control during the study and for at least 1 month following the last dose of study drug Female participants: • Women not of childbearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Women with an intact uterus are deemed postmenopausal if they are greater than or equal to 45 years old, who have not taken hormones or oral contraceptives within the last year, and had cessation of menses for at least 1 year, or who have had 6 to 12 months of amenorrhea with follicle-stimulating hormone (FSH) levels consistent with postmenopausal state. All participants: * have a screening body mass index (BMI) of 18.5 to 32.0 kilograms per square meter (kg/m\^2), inclusive * have clinical laboratory test results within the normal range for the population or investigator site, or with abnormalities deemed clinically insignificant by the investigator. In particular, participants should have normal or near normal screening liver tests at the discretion of the investigator * have normal blood pressure and pulse rate (supine) at screening, or with minor deviations judged to be acceptable by the investigator * have venous access sufficient to allow blood sampling as per the protocol * are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site
Exclusion criteria
All participants: * are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product other than the investigational product used in this study; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participants that participate in Part A of this study may participate in Part B of the study if the first dosing in Part B is \>30 days after the dose of LY2584702 or placebo in Part A. * have known allergies to LY2584702, or related compounds * have an abnormality in the 12-lead electrocardiogram (ECG) \[including but not limited to Bazett's corrected QT (QTcB) interval \>450 milliseconds (msec) for men and \>470 msec for women\] * have a history within the last 2 years 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 * have a history of drug or alcohol abuse, or regularly use known drugs of abuse * show evidence of human immunodeficiency virus infection and/or positive human immunodeficiency virus (HIV) antibodies * show evidence of hepatitis B and/or positive hepatitis B surface antigen * intend to use over-the-counter or prescription medication within 14 days prior to dosing or during the study * use of herbal supplements, grapefruit juice, grapefruits, Seville orange juice, Seville oranges, or Starfruit within 7 days prior to study dosing or intended use during the study * have donated blood of more than 450 milliliters (mL) within the last 3 months * have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or are unwilling to stop alcohol consumption from prior to dosing until the completion of each study period \[ unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits\] Applicable for Part A only: • have known allergies to lignocaine, adrenaline, tetracycline, or related compounds, which will be used in the skin biopsy procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose] | The Cmax following a single oral dose of LY2584702 test formulation \[TF (tablet)\] or reference formulation \[RF (capsule)\] is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose] | AUC from time 0 to the time of the last quantifiable concentration \[AUC(0-tlast)\] and AUC from time 0 to infinity \[AUC(0-inf)\] following a single oral dose of LY2584702 test formulation \[TF (tablet)\] or reference formulation \[RF (capsule)\] is reported. |
| Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | Part B: Baseline [Periods 1 and 4a (Day -1)], Periods 3, 4a (Day 1). Lipid concentration measurements were performed at time point 0 and 1 hour (h), 3 h, 4 h, 6 h, 10 h, and 24 h. | Baseline-adjusted change-from-predose in lipid concentrations were measured to assess the LY2584702 effect on lipids under different fed states. The 50-milligram (mg) LY2584702 test formulation \[TF (tablet)\] was the only dose and formulation administered in both the fasted and fed states for comparison. Therefore, changes in total cholesterol after single oral doses of placebo, 10-mg, or 200-mg LY2584702 TF or 25-mg or 50-mg LY2584702 reference formulation \[RF (capsule)\] were not calculated. The baseline-adjusted change-from-predose in total cholesterol levels in the fasted and fed state following a single 50-mg LY2584702 TF dose is reported. Baseline was Day -1 of Period 1 for Period 3 fasted state and baseline was Day -1 of Period 4a for Period 4a fed state. Least squares (LS) means was calculated using mixed model repeating measures (MMRM) and adjusted for treatment, time, treatment by time, and participant. |
| Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Part A: Baseline [Day 1 (Predose)] and Day 1 (3 h, 4 h, 6 h, and 24 h postdose) | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and is calculated from electrocardiogram (ECG) data. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between 2 R waves. Using Fridericia's formula: QTcF = QT/RR\^0.33. The QTcF after single oral doses of LY2584702 reference formulation \[RF (capsule)\] were administered in a fasted state are reported at baseline (Day 1, Predose) and 3 hours (h), 4 h, 6 h, and 24 h postdose. |
| Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Part B: Baseline [Period 1 (Day -1)] and Periods 1 to 4 (Day 1). Electrocardiograms (ECG) were performed at time point 0 and 3 h, 4 h, 6 h, and 24 h. | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and is calculated from electrocardiogram (ECG) data. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between 2 R waves. Using Fridericia's formula: QTcF = QT/RR\^0.33. The QTcF after single oral doses of LY2584702 test formulation \[TF (tablet)\], LY2584702 reference formulation \[RF (capsule)\], or placebo were administered in a fasted or fed state are reported at baseline (time-matched Day -1 QTcF) and 3 hours (h), 4 h, 6 h, and 24 h postdose. Day 1, Hour 24 was time-matched with Day-1, Hour 0. |
Countries
Singapore
Participant flow
Pre-assignment details
Part A: single period, single dose pilot assessed safety, tolerability. Part B: 4-period crossover evaluated bioavailability of 2 drug formulations. Part B, Period (P) 4 participants (pts) separated into 2 cohorts, received drug under fed (P4a) or fasted (P4b) conditions. Pts who withdrew or were withdrawn prior to completing P3 were replaced.
Participants by arm
| Arm | Count |
|---|---|
| Part A (LY2584702) Participants enrolled in Part A of the study received a single dose of 25 milligrams (mg) LY2584702 (LY) reference formulation \[RF (capsule)\] in a fasted state on Day 1. | 8 |
| Part A (Placebo) Participants enrolled in Part A of the study received placebo in a fasted state on Day 1. | 2 |
| 10 mg LY TF, Placebo, 50 mg LY TF, 50 mg LY TF Fed Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 test formulation \[TF (tablet)\], placebo, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods. | 2 |
| Placebo, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed Participants enrolled in Part B of the study received a single dose of placebo, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods. | 1 |
| Placebo, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted Participants enrolled in Part B of the study received a single dose of placebo, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods. | 3 |
| 10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 50 mg LY2584702 TF in a fed state in Period 4a, Day 1. There was a washout of at least 3 days between periods. | 7 |
| 10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods. | 3 |
| 10 mg LY TF, 50 mg LY RF, 50 mg LY TF, Placebo Fasted Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and 50 mg LY2584702 TF in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and placebo in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods. | 1 |
| 10 mg LY TF, 50 mg LY RF, Placebo, 200 mg LY TF Fasted Participants enrolled in Part B of the study received a single dose of 10 mg LY2584702 TF, 50 mg LY2584702 RF, and placebo in a fasted state, on Day 1 of Periods 1, 2, and 3, respectively and 200 mg LY2584702 TF in a fasted state in Period 4b, Day 1. There was a washout of at least 3 days between periods. | 1 |
| 200 mg LY TF Fasted Participant enrolled in Part B, Period 4b of the study received a single dose of 200 mg LY2584702 TF in a fasted state on Day 1. | 1 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Washout Period 2 | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Washout Period 3 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A (LY2584702) | Part A (Placebo) | 10 mg LY TF, Placebo, 50 mg LY TF, 50 mg LY TF Fed | Placebo, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed | Placebo, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted | 10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 50 mg LY TF Fed | 10 mg LY TF, 50 mg LY RF, 50 mg LY TF, 200 mg LY TF Fasted | 10 mg LY TF, 50 mg LY RF, 50 mg LY TF, Placebo Fasted | 10 mg LY TF, 50 mg LY RF, Placebo, 200 mg LY TF Fasted | 200 mg LY TF Fasted | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.9 years STANDARD_DEVIATION 7.3 | 24 years STANDARD_DEVIATION 4.2 | 44 years STANDARD_DEVIATION 25.5 | 39 years | 28 years STANDARD_DEVIATION 8.2 | 34 years STANDARD_DEVIATION 6.1 | 34 years STANDARD_DEVIATION 8.9 | 28 years | 35 years | 28 years | 32.6 years STANDARD_DEVIATION 8.8 |
| Race/Ethnicity, Customized Asian | 8 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 7 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 29 Participants |
| Region of Enrollment Singapore | 8 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 7 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 29 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 7 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 29 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 10 | 6 / 8 | 5 / 12 | 3 / 14 | 2 / 16 | 4 / 8 | 4 / 7 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 12 | 0 / 14 | 0 / 16 | 0 / 8 | 0 / 7 |
Outcome results
Primary
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)
The Cmax following a single oral dose of LY2584702 test formulation \[TF (tablet)\] or reference formulation \[RF (capsule)\] is reported.
Time frame: Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose]
Population: Randomized participants in Part A or B of the study who had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 25 mg LY2584702 RF Fasted | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 266.83 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71 |
| 10 mg LY2584702 TF Fasted | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 198.22 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| 50 mg LY2584702 RF Fasted | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 481.11 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| 50 mg LY2584702 TF Fasted | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 668.87 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| 50 mg LY2584702 TF Fed | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 794.13 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| 200 mg LY2584702 TF Fasted | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 1486.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 11 |
Secondary
Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and is calculated from electrocardiogram (ECG) data. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between 2 R waves. Using Fridericia's formula: QTcF = QT/RR\^0.33. The QTcF after single oral doses of LY2584702 reference formulation \[RF (capsule)\] were administered in a fasted state are reported at baseline (Day 1, Predose) and 3 hours (h), 4 h, 6 h, and 24 h postdose.
Time frame: Part A: Baseline [Day 1 (Predose)] and Day 1 (3 h, 4 h, 6 h, and 24 h postdose)
Population: Randomized participants in Part A of the study who had both baseline and postdose ECG assessments at each time point. Data was not collected for Placebo group due to insufficient participants (N=2).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg LY2584702 RF Fasted | Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | 6-hours postdose | 395.7 milliseconds (ms) | Standard Deviation 12.8 |
| 25 mg LY2584702 RF Fasted | Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Predose (Baseline) | 402.8 milliseconds (ms) | Standard Deviation 14.4 |
| 25 mg LY2584702 RF Fasted | Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | 3-hours postdose | 394.8 milliseconds (ms) | Standard Deviation 12.6 |
| 25 mg LY2584702 RF Fasted | Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | 4-hours postdose | 396.6 milliseconds (ms) | Standard Deviation 10.7 |
| 25 mg LY2584702 RF Fasted | Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | 24-hours postdose | 396.1 milliseconds (ms) | Standard Deviation 10.6 |
Secondary
Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and is calculated from electrocardiogram (ECG) data. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between 2 R waves. Using Fridericia's formula: QTcF = QT/RR\^0.33. The QTcF after single oral doses of LY2584702 test formulation \[TF (tablet)\], LY2584702 reference formulation \[RF (capsule)\], or placebo were administered in a fasted or fed state are reported at baseline (time-matched Day -1 QTcF) and 3 hours (h), 4 h, 6 h, and 24 h postdose. Day 1, Hour 24 was time-matched with Day-1, Hour 0.
Time frame: Part B: Baseline [Period 1 (Day -1)] and Periods 1 to 4 (Day 1). Electrocardiograms (ECG) were performed at time point 0 and 3 h, 4 h, 6 h, and 24 h.
Population: Randomized participants in Part B of the study who had both baseline and postdose ECG assessments at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 3 (time-matched baseline) | 416.1 milliseconds (ms) | Standard Deviation 21 |
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 24 | 415.4 milliseconds (ms) | Standard Deviation 19.4 |
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 4 (time-matched baseline) | 415.5 milliseconds (ms) | Standard Deviation 20.6 |
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 6 | 413.2 milliseconds (ms) | Standard Deviation 14.8 |
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 0 | 416.4 milliseconds (ms) | Standard Deviation 17.8 |
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 3 | 413.6 milliseconds (ms) | Standard Deviation 17.8 |
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 6 (time-matched baseline) | 417.1 milliseconds (ms) | Standard Deviation 20.6 |
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 0 (time-matched baseline) | 419.1 milliseconds (ms) | Standard Deviation 21 |
| 25 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 4 | 414.8 milliseconds (ms) | Standard Deviation 17.7 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 4 | 412.0 milliseconds (ms) | Standard Deviation 21 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 3 | 410.6 milliseconds (ms) | Standard Deviation 23.2 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 4 (time-matched baseline) | 413.1 milliseconds (ms) | Standard Deviation 20.7 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 0 (time-matched baseline) | 413.6 milliseconds (ms) | Standard Deviation 21.5 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 24 | 408.9 milliseconds (ms) | Standard Deviation 19 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 6 | 410.6 milliseconds (ms) | Standard Deviation 18.1 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 6 (time-matched baseline) | 415.0 milliseconds (ms) | Standard Deviation 19.8 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 0 | 413.3 milliseconds (ms) | Standard Deviation 23 |
| 10 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 3 (time-matched baseline) | 412.4 milliseconds (ms) | Standard Deviation 19.8 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 4 | 409.2 milliseconds (ms) | Standard Deviation 14 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 4 (time-matched baseline) | 414.6 milliseconds (ms) | Standard Deviation 18.3 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 0 (time-matched baseline) | 417.1 milliseconds (ms) | Standard Deviation 18.9 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 0 | 414.4 milliseconds (ms) | Standard Deviation 17.7 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 3 (time-matched baseline) | 413.8 milliseconds (ms) | Standard Deviation 18.2 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 3 | 409.2 milliseconds (ms) | Standard Deviation 16.2 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 6 (time-matched baseline) | 417.6 milliseconds (ms) | Standard Deviation 19.3 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 6 | 409.6 milliseconds (ms) | Standard Deviation 14.3 |
| 50 mg LY2584702 RF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 24 | 409.1 milliseconds (ms) | Standard Deviation 13.9 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 0 (time-matched baseline) | 428.0 milliseconds (ms) | Standard Deviation 11.2 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 0 | 407.8 milliseconds (ms) | Standard Deviation 16.2 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 24 | 411.1 milliseconds (ms) | Standard Deviation 13.5 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 6 (time-matched baseline) | 420.5 milliseconds (ms) | Standard Deviation 12.5 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 6 | 414.8 milliseconds (ms) | Standard Deviation 11.5 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 3 (time-matched baseline) | 423.3 milliseconds (ms) | Standard Deviation 14.8 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 3 | 402.6 milliseconds (ms) | Standard Deviation 10 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 4 | 407.3 milliseconds (ms) | Standard Deviation 12.1 |
| 50 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 4 (time-matched baseline) | 420.7 milliseconds (ms) | Standard Deviation 10.1 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 6 (time-matched baseline) | 422.3 milliseconds (ms) | Standard Deviation 24 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 4 (time-matched baseline) | 418.3 milliseconds (ms) | Standard Deviation 24.2 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 3 (time-matched baseline) | 415.2 milliseconds (ms) | Standard Deviation 22 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 0 | 413.1 milliseconds (ms) | Standard Deviation 22.1 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 4 | 413.3 milliseconds (ms) | Standard Deviation 20.4 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 0 (time-matched baseline) | 415.8 milliseconds (ms) | Standard Deviation 23.5 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 24 | 409.0 milliseconds (ms) | Standard Deviation 17.9 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 6 | 415.6 milliseconds (ms) | Standard Deviation 15.8 |
| 50 mg LY2584702 TF Fed | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 3 | 409.9 milliseconds (ms) | Standard Deviation 22.1 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 3 (time-matched baseline) | 415.7 milliseconds (ms) | Standard Deviation 14.2 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 3 | 412.3 milliseconds (ms) | Standard Deviation 17.8 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 6 | 412.4 milliseconds (ms) | Standard Deviation 16.6 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 4 | 415.2 milliseconds (ms) | Standard Deviation 19.3 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 0 | 412.1 milliseconds (ms) | Standard Deviation 19.8 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 6 (time-matched baseline) | 418.1 milliseconds (ms) | Standard Deviation 16.8 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 0 (time-matched baseline) | 416.4 milliseconds (ms) | Standard Deviation 19.2 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day 1, Hour 24 | 409.0 milliseconds (ms) | Standard Deviation 19.8 |
| 200 mg LY2584702 TF Fasted | Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1 | Day-1, Hour 4 (time-matched baseline) | 413.4 milliseconds (ms) | Standard Deviation 17.1 |
Secondary
Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol)
Baseline-adjusted change-from-predose in lipid concentrations were measured to assess the LY2584702 effect on lipids under different fed states. The 50-milligram (mg) LY2584702 test formulation \[TF (tablet)\] was the only dose and formulation administered in both the fasted and fed states for comparison. Therefore, changes in total cholesterol after single oral doses of placebo, 10-mg, or 200-mg LY2584702 TF or 25-mg or 50-mg LY2584702 reference formulation \[RF (capsule)\] were not calculated. The baseline-adjusted change-from-predose in total cholesterol levels in the fasted and fed state following a single 50-mg LY2584702 TF dose is reported. Baseline was Day -1 of Period 1 for Period 3 fasted state and baseline was Day -1 of Period 4a for Period 4a fed state. Least squares (LS) means was calculated using mixed model repeating measures (MMRM) and adjusted for treatment, time, treatment by time, and participant.
Time frame: Part B: Baseline [Periods 1 and 4a (Day -1)], Periods 3, 4a (Day 1). Lipid concentration measurements were performed at time point 0 and 1 hour (h), 3 h, 4 h, 6 h, 10 h, and 24 h.
Population: Randomized participants (pts) in Part B of study who had both baseline and postdose total cholesterol measurements. Pts not analyzed for baseline-adjusted change-from-predose total cholesterol levels after single dose placebo, 10-mg, or 200-mg LY2584702 TF or 25-mg or 50-mg LY2584702 RF since they weren't administered in both fasted and fed state.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 25 mg LY2584702 RF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 6-hours postdose | -4.77 milligrams per deciliter (mg/dL) |
| 25 mg LY2584702 RF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 1-hour postdose | -5.62 milligrams per deciliter (mg/dL) |
| 25 mg LY2584702 RF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 10-hours postdose | -9.23 milligrams per deciliter (mg/dL) |
| 25 mg LY2584702 RF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 4-hours postdose | -4.15 milligrams per deciliter (mg/dL) |
| 25 mg LY2584702 RF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 24-hours postdose | -8.85 milligrams per deciliter (mg/dL) |
| 25 mg LY2584702 RF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 3-hours postdose | -4.00 milligrams per deciliter (mg/dL) |
| 10 mg LY2584702 TF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 24-hours postdose | -8.75 milligrams per deciliter (mg/dL) |
| 10 mg LY2584702 TF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 3-hours postdose | -1.75 milligrams per deciliter (mg/dL) |
| 10 mg LY2584702 TF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 4-hours postdose | -1.88 milligrams per deciliter (mg/dL) |
| 10 mg LY2584702 TF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 6-hours postdose | 0.75 milligrams per deciliter (mg/dL) |
| 10 mg LY2584702 TF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 10-hours postdose | -5.25 milligrams per deciliter (mg/dL) |
| 10 mg LY2584702 TF Fasted | Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol) | 1-hour postdose | -2.38 milligrams per deciliter (mg/dL) |
Secondary
Pharmacokinetics, Area Under the Concentration-Time Curve (AUC)
AUC from time 0 to the time of the last quantifiable concentration \[AUC(0-tlast)\] and AUC from time 0 to infinity \[AUC(0-inf)\] following a single oral dose of LY2584702 test formulation \[TF (tablet)\] or reference formulation \[RF (capsule)\] is reported.
Time frame: Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose]
Population: Randomized participants in Part A or B of the study who had evaluable AUC data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 25 mg LY2584702 RF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-inf) | 1860 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 58 |
| 25 mg LY2584702 RF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-tlast) | 1740 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 63 |
| 10 mg LY2584702 TF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-tlast) | 1070 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 26 |
| 10 mg LY2584702 TF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-inf) | 1110 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 27 |
| 50 mg LY2584702 RF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-inf) | 3530 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 43 |
| 50 mg LY2584702 RF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-tlast) | 3310 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 43 |
| 50 mg LY2584702 TF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-tlast) | 4210 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
| 50 mg LY2584702 TF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-inf) | 4430 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
| 50 mg LY2584702 TF Fed | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-tlast) | 5560 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 30 |
| 50 mg LY2584702 TF Fed | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-inf) | 5620 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 29 |
| 200 mg LY2584702 TF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-tlast) | 10300 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 20 |
| 200 mg LY2584702 TF Fasted | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) | AUC(0-inf) | 10900 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 20 |