Insomnia
Conditions
Brief summary
The purpose of this study is to determine the effect of activated charcoal and dosing time on the absorption of LY2624803 in healthy subjects. In this crossover study, there are three treatments with a washout period of at least 7 days in between treatments. Each subject will participate in all three treatments with random assignment to the treatment sequence.
Interventions
DRUGLY2624803
Administered orally (po), once.
OTHERActivated Charcoal
Administered po
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy males or females, as determined by medical history and physical examination. * Male subjects with female partners of child-bearing potential and female subjects of child-bearing potential, agree to use 2 reliable methods of contraception from the time of the first dose until 3 months after the last dose of study drug or are women not of child-bearing potential due to postmenopausal or permanently sterilized \[for example, tubal occlusion, hysterectomy, bilateral salpingectomy\]). * Have a body mass index (BMI) between 18.5 and 32 kilograms per square meter (kg/m2), inclusive, and a body weight of 50 kg or above at screening. * 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 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 governing the site.
Exclusion criteria
* Are currently enrolled in, or discontinued within the last 90 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 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 LY2624803 or related compounds. * Are persons who have previously completed or withdrawn from this study or any other study investigating LY2624803. * 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 an abnormal blood pressure as determined by the investigator. * Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (except appendectomy), endocrine, hematological, dermatological, venereal, 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. * Show evidence or history of postural hypotension, loss of consciousness, explained or unexplained syncope or seizure episodes or a family history of seizures. A history of a single febrile convulsion is acceptable. * Show evidence of significant active neuropsychiatric disease. * 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 medications, with the exception of vitamins and paracetamol, which cannot be safely discontinued within 7 days prior to admission. * Have donated blood of more than 500 milliliters (mL) within the last 3 months prior to screening. * Have an average weekly alcohol intake that exceeds 28 units per week (males) and 21 units per week (females), and are subjects unwilling to stop alcohol consumption from 48 hours prior to admission until discharge from the unit for each treatment period, and to limit alcohol intake to a maximum of 2 units/day between treatment periods. * Have a history of breast cancer. * Are subjects with excessive xanthine consumption. * Exhibit any other condition, which, in the opinion of the investigator would preclude participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve (AUC) for LY2624803 and the Metabolite LSN2797276 | Predose and up to Day 4 | AUC from time 0, extrapolated to infinity, estimated for both LY2624803 and the metabolite LSN2797276. |
| Maximum Concentration (Cmax) for LY2624803 and the Metabolite, LSN2797276, | Predose and up to Day 4 | Cmax estimated for both LY2624803 and the metabolite LSN2797276. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma Concentration (Tmax) for LY2624803 and the Metabolite, LSN2797276 | Predose and up to day 4 | Tmax, estimated for both LY2624803 and the metabolite LSN2797276. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2624803 Participants received each of the following 3 study treatments:
LY2624803 Alone Morning Dosing: Participants received 6 milligrams (mg) LY2624803 alone, orally (po) once at approximately 0800 hours following an overnight fast.
LY2624803 Morning Dosing Plus Activated Charcoal: Participants received 6 mg LY2624803 po once at approximately 0800 hours following an overnight fast, followed 1 hour later by a single po dose of 1 gram per kilogram (g/kg) body weight of activated charcoal, mixed with caffeine-free diet cola.
LY2624803 Alone Evening Dosing: Participants received 6 mg LY2624803 alone po once at approximately 2200 hours following a 4-hour fast. | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | LY2624803 |
|---|---|
| Age Continuous | 32.3 years STANDARD_DEVIATION 11.7 |
| Race/Ethnicity, Customized Black | 1 participants |
| Race/Ethnicity, Customized White | 20 participants |
| Region of Enrollment United Kingdom | 21 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 17 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 | 13 / 21 | 8 / 21 | 10 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 | 0 / 21 |
Outcome results
Primary
Area Under the Concentration-Time Curve (AUC) for LY2624803 and the Metabolite LSN2797276
AUC from time 0, extrapolated to infinity, estimated for both LY2624803 and the metabolite LSN2797276.
Time frame: Predose and up to Day 4
Population: All participants who received at least 1 dose of LY2624803 and have evaluable pharmacokinetic (PK) data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2624803 Alone Morning Dosing | Area Under the Concentration-Time Curve (AUC) for LY2624803 and the Metabolite LSN2797276 | LY2624803 | 5240 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 30 |
| LY2624803 Alone Morning Dosing | Area Under the Concentration-Time Curve (AUC) for LY2624803 and the Metabolite LSN2797276 | LSN2797276 (N=18, 12, 15) | 192 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 23 |
| LY2624803 Morning Dosing Plus Activated Charcoal | Area Under the Concentration-Time Curve (AUC) for LY2624803 and the Metabolite LSN2797276 | LY2624803 | 3340 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 30 |
| LY2624803 Morning Dosing Plus Activated Charcoal | Area Under the Concentration-Time Curve (AUC) for LY2624803 and the Metabolite LSN2797276 | LSN2797276 (N=18, 12, 15) | 112 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 19 |
| LY2624803 Alone Evening Dosing | Area Under the Concentration-Time Curve (AUC) for LY2624803 and the Metabolite LSN2797276 | LY2624803 | 4620 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 30 |
| LY2624803 Alone Evening Dosing | Area Under the Concentration-Time Curve (AUC) for LY2624803 and the Metabolite LSN2797276 | LSN2797276 (N=18, 12, 15) | 188 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 26 |
Primary
Maximum Concentration (Cmax) for LY2624803 and the Metabolite, LSN2797276,
Cmax estimated for both LY2624803 and the metabolite LSN2797276.
Time frame: Predose and up to Day 4
Population: All participants who received at least 1 dose of LY2624803 and have evaluable pharmacokinetic (PK) data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2624803 Alone Morning Dosing | Maximum Concentration (Cmax) for LY2624803 and the Metabolite, LSN2797276, | LY2624803 | 368 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| LY2624803 Alone Morning Dosing | Maximum Concentration (Cmax) for LY2624803 and the Metabolite, LSN2797276, | LSN2797276 | 6.22 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| LY2624803 Morning Dosing Plus Activated Charcoal | Maximum Concentration (Cmax) for LY2624803 and the Metabolite, LSN2797276, | LY2624803 | 335 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| LY2624803 Morning Dosing Plus Activated Charcoal | Maximum Concentration (Cmax) for LY2624803 and the Metabolite, LSN2797276, | LSN2797276 | 5.11 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| LY2624803 Alone Evening Dosing | Maximum Concentration (Cmax) for LY2624803 and the Metabolite, LSN2797276, | LY2624803 | 273 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| LY2624803 Alone Evening Dosing | Maximum Concentration (Cmax) for LY2624803 and the Metabolite, LSN2797276, | LSN2797276 | 5.94 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Secondary
Time to Maximum Plasma Concentration (Tmax) for LY2624803 and the Metabolite, LSN2797276
Tmax, estimated for both LY2624803 and the metabolite LSN2797276.
Time frame: Predose and up to day 4
Population: All participants who received at least 1 dose of LY2624803 and have evaluable pharmacokinetic (PK) data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LY2624803 Alone Morning Dosing | Time to Maximum Plasma Concentration (Tmax) for LY2624803 and the Metabolite, LSN2797276 | LY2624803 | 1.50 hours (h) |
| LY2624803 Alone Morning Dosing | Time to Maximum Plasma Concentration (Tmax) for LY2624803 and the Metabolite, LSN2797276 | LSN2797276 | 4.00 hours (h) |
| LY2624803 Morning Dosing Plus Activated Charcoal | Time to Maximum Plasma Concentration (Tmax) for LY2624803 and the Metabolite, LSN2797276 | LY2624803 | 0.75 hours (h) |
| LY2624803 Morning Dosing Plus Activated Charcoal | Time to Maximum Plasma Concentration (Tmax) for LY2624803 and the Metabolite, LSN2797276 | LSN2797276 | 4.00 hours (h) |
| LY2624803 Alone Evening Dosing | Time to Maximum Plasma Concentration (Tmax) for LY2624803 and the Metabolite, LSN2797276 | LY2624803 | 2.00 hours (h) |
| LY2624803 Alone Evening Dosing | Time to Maximum Plasma Concentration (Tmax) for LY2624803 and the Metabolite, LSN2797276 | LSN2797276 | 8.00 hours (h) |