Major Depressive Disorder
Conditions
Brief summary
The purpose of this study is to determine how much digoxin gets into the blood stream and how long it takes the body to get rid of it when given with LY2216684. Information about any side effects that may occur will also be collected.
Interventions
DRUGLY2216684
Administered orally
DRUGDigoxin
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
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 participants - Agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. * Female participants - 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 6 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 or bilateral oophorectomy or tubal ligation) or menopause (at least 1 year without menses or 6 months without menses and a follicle stimulating hormone \[FSH\] greater than (\>) 40 milli-International Units/milliliter (mIU/mL). * Have a body weight \>50 kilograms (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 (potassium, magnesium, and calcium values must be within the normal range). * Have normal renal function defined as an estimated creatinine clearance of at least 80 milliliters/minute (mL/min) as calculated with the Cockcroft-Gault equation. * Have venous access sufficient to allow blood sampling as per the protocol. * Have normal blood pressure and pulse rate (sitting position) as determined by the investigator. * 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
* Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device other than the study drug, 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, digoxin, or related compounds. * Are persons who have previously 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 of significant dysrhythmias or atrioventricular (AV) block. * Have a history or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation. * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening. * Show evidence of human immunodeficiency virus (HIV) 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 (including hormonal contraceptives) within 14 days prior to dosing unless deemed acceptable by the investigator and Sponsor's medical monitor, except for influenza vaccinations. * Use of any drugs or substances that are known to be substrates, inducers, or inhibitors of P-glycoprotein (P-gp) and Cytochrome (P45) (CYP) within 30 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 14 units per week, or are unwilling to stop alcohol consumption 48 hours prior to check-in until completion of the study (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). * Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any participant unwilling to adhere to study caffeine restrictions. * Have used any tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to enrollment. * Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment and during the study. * Have a documented or suspected history of glaucoma. * Participants determined to be unsuitable by the investigator for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Digoxin: Maximum Plasma Concentration (Cmax) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14 | Cmax of digoxin when administered alone and when co-administered with LY2216684. |
| Pharmacokinetics of Digoxin: Time to Maximum Plasma Concentration (Tmax) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14 | Tmax of digoxin when administered alone and when co-administered with LY2216684. |
| Pharmacokinetics of Digoxin: Area Under the Concentration Time Curve at Steady State Over the Dosing Interval (AUCt) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14 | AUCt at steady state of digoxin when administered alone and when co-administered with LY2216684. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2216684 + Digoxin Two oral 0.5-milligrams (mg) (two 0.25-mg tablets) doses of digoxin separated by 12 hours on Day 1, followed by once daily 0.25-mg (single 0.25-mg tablet) dose of digoxin on Days 2-14. Daily oral 18-mg (two 9-mg tablets) doses of LY2216684 on Days 8-14. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | LY2216684 + Digoxin |
|---|---|
| Age, Continuous | 34.9 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 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 | 5 Participants |
| Race (NIH/OMB) More than one race | 2 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 | 23 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 18 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 | 3 / 30 | 4 / 28 | 16 / 27 |
| serious Total, serious adverse events | 0 / 30 | 0 / 28 | 0 / 27 |
Outcome results
Primary
Pharmacokinetics of Digoxin: Area Under the Concentration Time Curve at Steady State Over the Dosing Interval (AUCt)
AUCt at steady state of digoxin when administered alone and when co-administered with LY2216684.
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14
Population: All participants who received at least 1 dose of study drug and evaluable AUCt values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Digoxin | Pharmacokinetics of Digoxin: Area Under the Concentration Time Curve at Steady State Over the Dosing Interval (AUCt) | 14.6 hours*nanograms/milliliter (h*ng/mL) |
| LY2216684 + Digoxin | Pharmacokinetics of Digoxin: Area Under the Concentration Time Curve at Steady State Over the Dosing Interval (AUCt) | 14.3 hours*nanograms/milliliter (h*ng/mL) |
Primary
Pharmacokinetics of Digoxin: Maximum Plasma Concentration (Cmax)
Cmax of digoxin when administered alone and when co-administered with LY2216684.
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14
Population: All participants who received at least 1 dose of study drug and had evaluable Cmax values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Digoxin | Pharmacokinetics of Digoxin: Maximum Plasma Concentration (Cmax) | 1.433 nanograms/milliliter (ng/mL) |
| LY2216684 + Digoxin | Pharmacokinetics of Digoxin: Maximum Plasma Concentration (Cmax) | 1.424 nanograms/milliliter (ng/mL) |
Primary
Pharmacokinetics of Digoxin: Time to Maximum Plasma Concentration (Tmax)
Tmax of digoxin when administered alone and when co-administered with LY2216684.
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14
Population: All participants who received at least 1 dose of study drug and had evaluable Tmax values.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Digoxin | Pharmacokinetics of Digoxin: Time to Maximum Plasma Concentration (Tmax) | 2.00 hours |
| LY2216684 + Digoxin | Pharmacokinetics of Digoxin: Time to Maximum Plasma Concentration (Tmax) | 1.00 hours |
p-value: 0.0664Wilcoxon Signed Rank