Depressive Disorder, Major
Conditions
Brief summary
The study involves a single oral dose of 18 mg (2 x 9mg tablets) LY2216684 taken on 2 occasions, once with activated charcoal and once without activated charcoal. The study will evaluate the effect of charcoal on the absorption of LY2216684. Side effects will be documented. 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
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
* Are overtly healthy, as determined by medical history and physical examination \- Male subjects: Agree to use a reliable method of birth control during the study and for 1 month following the last dose of the 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 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 or 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 \[milli-international-units/milliliter\]) * Have a body weight \>50 kg * 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)
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 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 * Have a history or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation * Have a documented or suspected history of glaucoma * 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 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. Exceptions include influenza vaccinations, the use of topical medication (provided there is no evidence of chronic dosing with the risk of systemic exposure), occasional use of acetaminophen/paracetamol/ibuprofen, hormone replacement therapy including thyroid replacement (stable dose for at least 1 month), and stable doses (at least 1 month) of oral contraceptive therapy * 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 unwilling to adhere to the smoking restrictions of the Clinical Research Unit (CRU) while a resident of the CRU. * Have consumed grapefruit or grapefruit-containing products 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684 | Predose, up to 72 hours after administration of study drug | The AUC0-∞ of LY2216684 was measured. The AUC was calculated for LY2216684 administered alone (reference) and LY2216684 co-administered with charcoal (test). Geometric Least Squares (LS) means were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for AUC. |
| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 | Predose, up to 72 hours after administration of study drug | The Cmax of LY2216684 was assessed. The Cmax was calculated for LY2216684 administered alone (reference) and LY2216684 co-administered with charcoal (test). Geometric LSMeans 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 | Predose, up to 72 hours after administration of study drug | The tmax for LY2216684 was assessed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall During Study Period 1, participants received a single oral dose of 18 mg LY2216684 alone or in combination with 1 g/kg Activated Charcoal 1 hour after LY2216684 administration. After at least 7 days, participants who initially received 18 mg LY2216684 alone received another single oral dose of 18 mg LY2216684 in combination with 1 g/kg Activated Charcoal 1 hour after LY2216684 administration during Study Period 2; participants who initially received 18 mg LY2216684 in combination with 1 g/kg Activated Charcoal received another single oral dose of 18 mg LY2216684 alone during Study Period 2. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Study Period 1 | Sponsor decision | 0 | 2 |
| Study Period 2 | Sponsor decision | 1 | 0 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 35.2 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 15 Participants |
| Region of Enrollment United States | 22 Participants |
| Sex: Female, Male Female | 11 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 | 9 / 22 | 7 / 20 |
| serious Total, serious adverse events | 0 / 22 | 0 / 20 |
Outcome results
Primary
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684
The AUC0-∞ of LY2216684 was measured. The AUC was calculated for LY2216684 administered alone (reference) and LY2216684 co-administered with charcoal (test). Geometric Least Squares (LS) means were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for AUC.
Time frame: Predose, up to 72 hours after administration of study drug
Population: All participants who were randomized, for whom AUC0-∞ data were available, and who were not excluded due to vomiting within twice the median time to maximum plasma concentration (tmax) of LY2216684.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| LY2216684 in Combination With Activated Charcoal | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684 | 509 nanogram*hour/milliliter (ng*h/mL) |
| LY2216684 Alone | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684 | 786 nanogram*hour/milliliter (ng*h/mL) |
90% CI: [0.61, 0.68]Mixed Models Analysis
Primary
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684
The Cmax of LY2216684 was assessed. The Cmax was calculated for LY2216684 administered alone (reference) and LY2216684 co-administered with charcoal (test). Geometric LSMeans were calculated according to the following model: Log(PK) = sequence + period + treatment + subject + random error for Cmax.
Time frame: Predose, up to 72 hours after administration of study drug
Population: All participants who were randomized, for whom Cmax data were available, and who were not excluded due to vomiting within twice the median time to maximum plasma concentration (tmax) of LY2216684.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| LY2216684 in Combination With Activated Charcoal | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 | 54.06 nanogram/milliliter (ng/mL) |
| LY2216684 Alone | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 | 59.84 nanogram/milliliter (ng/mL) |
90% CI: [0.83, 0.98]Mixed Models Analysis
Primary
Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684
The tmax for LY2216684 was assessed.
Time frame: Predose, up to 72 hours after administration of study drug
Population: All participants who were randomized, for whom tmax data were available, and who were not excluded due to vomiting within twice the median tmax of LY2216684.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2216684 in Combination With Activated Charcoal | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684 | 2.00 hours |
| LY2216684 Alone | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684 | 2.03 hours |
p-value: 0.00190% CI: [-1.04, -0.5]Wilcoxon (Mann-Whitney)