Depressive Disorder, Major
Conditions
Brief summary
This study will evaluate the effect of food on LY2216684. There will be 2 study periods each lasting up to 5 days. There will be at least 7 days between the two doses and a follow up will occur at least 7 days after the last dose. Screening is required within 30 days prior to the start of the study.
Interventions
DRUGLY2216684
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male subjects: Agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. * Female subjects: Are women of child-bearing potential who test negative for pregnancy at the time of enrollment, have used a reliable method of birth control for 4 weeks prior to administration of study drug, and agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; or women not of child-bearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation) or menopause \[at least 1 year without menses or 6 months without menses and a follicle stimulating hormone (FSH) \>40 mIU/mL (milli-international-units/milliliter)\] * All Subjects: * Are overtly healthy as determined by medical history and physical examination * Have a body weight \>50 kg (kilogram) * 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 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 institutional review board (IRB) governing the site * Have normal blood pressure (BP) and pulse rate (sitting position) * Are willing to eat all components in the standard high-fat meal
Exclusion criteria
* 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 * Have known allergies to LY2216684, related compounds, or any components of the formulation * Are persons who have previously received the investigational product in this study, have completed or withdrawn from this study or any other study investigating LY2216684 within 6 months prior to Screening * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study * Have a history of suicidal ideation or suicide attempts * Have a history of/or current 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 or prescription medication within 14 days prior to dosing unless deemed acceptable by the investigator and sponsor's medical monitor, except for influenza vaccinations * Have donated blood of more than 500 mL (milliliter) within the last month * Have an average weekly alcohol intake that exceeds 21 units per week (males) or 14 units per week (females), or are unwilling to stop alcohol consumption from 48 hours prior to dosing in each period until discharge in each period \[1 unit = 12 oz (ounces) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits\] * Consume 5 or more cups of coffee (or other beverages or foods of comparable caffeine content) per day, on a habitual basis, or are unwilling to stop caffeine consumption from 48 hours prior to dosing in each period until discharge in each period * Subjects must adhere to the smoking restrictions of the Clinical Research Unit (CRU) while a resident of the CRU * Have consumed grapefruit or grapefruit-containing products, starfruit, or pomegranates 7 days prior to enrollment or are unwilling to avoid them during the study * Subjects determined to be unsuitable by the investigator for any reason * Have a documented or suspected history of glaucoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684 | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 24, 48, 72 hours post dose | The AUC for LY2216684 was calculated for LY2216684 administered in fed state (test) and LY2216684 administered in fasted state (reference). Geometric Least Squares (LS) means were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for AUC. |
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2216684 | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 24, 48, 72 hours post dose | The Cmax for LY2216684 was calculated for LY2216684 administered in fed state (test) and LY2216684 administered in fasted state (reference). Geometric LS means were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for Cmax. |
| Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684 | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 24, 48, 72 hours post dose | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall In Period 1, participants received a single oral dose of 18 milligram (mg) LY2216684, administered in either fasted or fed state. In Period 2, participants received a single oral dose of 18 mg LY2216684, administered in the alternative feeding state that was not used during Period 1 (fasted or fed). Periods were separated by a 7-day washout period. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 24 | 6 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684
The AUC for LY2216684 was calculated for LY2216684 administered in fed state (test) and LY2216684 administered in fasted state (reference). Geometric Least Squares (LS) means were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for AUC.
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 24, 48, 72 hours post dose
Population: All participants with a baseline observation and at least 1 post-baseline observation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| LY2216684 Administered in Fed State | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684 | 871 nanogram*hour/milliliter (ng*h/mL) |
| LY2216684 Administered in Fasted State | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684 | 861 nanogram*hour/milliliter (ng*h/mL) |
90% CI: [0.97, 1.05]Mixed Models Analysis
Primary
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2216684
The Cmax for LY2216684 was calculated for LY2216684 administered in fed state (test) and LY2216684 administered in fasted state (reference). Geometric LS means were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for Cmax.
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 24, 48, 72 hours post dose
Population: All participants with a baseline observation and at least 1 post-baseline observation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| LY2216684 Administered in Fed State | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2216684 | 66.04 nanogram/milliliter (ng/mL) |
| LY2216684 Administered in Fasted State | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2216684 | 68.68 nanogram/milliliter (ng/mL) |
90% CI: [0.92, 1.01]Mixed Models Analysis
Primary
Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 24, 48, 72 hours post dose
Population: All participants with a baseline observation and at least 1 post-baseline observation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2216684 Administered in Fed State | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684 | 3.00 hours |
| LY2216684 Administered in Fasted State | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684 | 2.00 hours |
p-value: 0.003190% CI: [0.5, 1.5]Wilcoxon (Mann-Whitney)