Healthy Volunteer Study
Conditions
Brief summary
The study will evaluate the effect of activated charcoal on absorption of LY2140023. The study involves a single dose of 80 milligrams (mg) LY2140023 taken as 1 tablet by mouth 2 times during study (once with activated charcoal, once without activated charcoal). This study will last approximately 16 days, not including screening. Screening is required within 28 days prior to study entry.
Interventions
DRUGLY2140023
DRUGAqueous activated charcoal
Sponsors
Denovo Biopharma LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* are healthy males or females, as determined by medical history and physical examination * male participants agree to use a reliable method of birth control during the study and for 3 months following the last dose of LY2140023, and agree not to donate sperm for 3 months following the last dose of LY2140023 * female participants: * of childbearing potential, who test negative for pregnancy at screening and who agree to use a reliable method of birth control during the study and for 3 months following the last dose of LY2140023 * of non-childbearing potential; postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy or confirmed tubal occlusion (not tubal ligation). Postmenopausal is defined as spontaneous amenorrhea for at least 12 months, and a plasma follicle-stimulating hormone (FSH) level \>40 milli-international units per milliliter(mIU/mL), unless the participant is taking hormone replacement therapy * have given written informed consent approved by Lilly and the chosen ethical review board (ERB)
Exclusion criteria
* are currently enrolled in, have completed or discontinued within the last 90 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 LY2140023 or LY404039, related compounds, activated charcoal, or any components of the formulation * are participants who have previously withdrawn from this study or any other study investigating LY2140023 after receiving at least 1 dose of LY2140023 * show evidence or any history of significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, depression) * have increased risk of seizures based on a history of: * one or more seizures (except for a single simple febrile seizure \[lacking focality and lasting less than 15 minutes, not associated with a central nervous system (CNS) infection or severe metabolic disturbance\] as a child between ages 6 months to 5 years) * head trauma with loss of consciousness or a post-concussive syndrome within 1 year or lifetime history of head trauma with persistent neurological deficit (focal or diffuse) * CNS infection, uncontrolled migraine, or transient ischemic attack (TIA) within 1 year; stroke with persistent neurological deficit (focal or diffuse). Uncontrolled migraine is defined as migraine attacks that produce headache lasting up to 72 hours and are often accompanied by associated symptoms (nausea, photophobia, and phonophobia) that impair well-being and disrupt social functioning. TIA is defined as mini-stroke caused by temporary disturbance of blood supply to an area of the brain, which results in a sudden, brief decrease in brain function * CNS infection with persistent neurological deficit (focal or diffuse) * brain surgery * electroencephalogram (EEG) with paroxysmal (epileptiform) activity (isolated spikes waves, repetitive bursts of sharp waves, paroxysmal activity, frank seizures, spike-wave complexes, or sharp-slow wave complexes, or as locally defined) * brain structural lesion, including developmental abnormalities, as determined by examination or imaging studies (except hydrocephalus treated by shunt and without neurological deficit) * show evidence of active renal disease (for example, diabetic renal disease, polycystic kidney disease) or creatinine clearance less than 90 milliliters per minute (mL/min) as determined by the Cockroft Gault formula * show evidence or any history of known substance dependence or abuse at any time (according to Diagnostic and Statistical Manual of Mental Disorders \[DSM-IV\] diagnosis), or regularly use known drugs of abuse and/or show positive findings on urinary drug screening * have a clinically significant abnormality in the neurological examination * participants judged prior to randomization to be at suicidal risk by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2140023 | Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose | Venous blood samples were collected for pharmacokinetic parameter estimates for LY2140023 alone and in the presence of aqueous activated charcoal. |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY2140023 | Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose | Venous blood samples were collected for pharmacokinetic parameter estimates for LY2140023 alone and in the presence of aqueous activated charcoal. |
| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY404039 (Active Moiety) | Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose | Venous blood samples were collected for pharmacokinetic parameter estimates for LY404039 alone and in the presence of aqueous activated charcoal. |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY404039 (Active Moiety) | Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose | Venous blood samples were collected for pharmacokinetic parameter estimates for LY404039 alone and in the presence of aqueous activated charcoal. |
Countries
United Kingdom
Participant flow
Pre-assignment details
This was a 2-period crossover study. Participants received single doses of LY2140023 on 2 different occasions: 1) LY2140023 administered alone (Treatment A) and 2) LY2140023 administered and followed 1 hour later by a single dose of aqueous activated charcoal (Treatment B). Participants were randomized to Treatment Sequence AB or BA.
Participants by arm
| Arm | Count |
|---|---|
| All Participants This was 2-period crossover study. Participants received single oral doses of LY2140023 on 2 different occasions: 1) 80 mg LY2140023 administered alone (Treatment A) and 2) 80 mg LY2140023 administered and followed 1 hour later by a single oral dose of 75 g aqueous activated charcoal (Treatment B). Participants were randomly assigned to treatment sequence AB or BA. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 3 | 5 |
| Period 1 | Sponsor Decision | 0 | 1 |
| Period 2 | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 29.1 years STANDARD_DEVIATION 14 |
| Race/Ethnicity, Customized Asian | 2 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants |
| Race/Ethnicity, Customized White | 24 participants |
| Region of Enrollment United Kingdom | 27 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 22 | 13 / 24 |
| serious Total, serious adverse events | 0 / 22 | 0 / 24 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY2140023
Venous blood samples were collected for pharmacokinetic parameter estimates for LY2140023 alone and in the presence of aqueous activated charcoal.
Time frame: Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Population: Participants who received study drug(s), did not have an incidence of vomiting following administration of LY2140023, and had evaluable AUC(0-inf) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY2140023 | 1120 nanogram hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 24 |
| 80 mg LY2140023 + 75 g Aqueous Activated Charcoal | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY2140023 | 876 nanogram hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 26 |
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY404039 (Active Moiety)
Venous blood samples were collected for pharmacokinetic parameter estimates for LY404039 alone and in the presence of aqueous activated charcoal.
Time frame: Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Population: Participants who received study drug(s), did not have an incidence of vomiting following administration of LY2140023, and had evaluable AUC(0-inf) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY404039 (Active Moiety) | 2780 ng*h/mL | Geometric Coefficient of Variation 15 |
| 80 mg LY2140023 + 75 g Aqueous Activated Charcoal | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of LY404039 (Active Moiety) | 2190 ng*h/mL | Geometric Coefficient of Variation 19 |
Primary
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2140023
Venous blood samples were collected for pharmacokinetic parameter estimates for LY2140023 alone and in the presence of aqueous activated charcoal.
Time frame: Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Population: Participants who received study drug(s), did not have an incidence of vomiting following administration of LY2140023, and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023 | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2140023 | 251 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| 80 mg LY2140023 + 75 g Aqueous Activated Charcoal | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2140023 | 171 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
Primary
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY404039 (Active Moiety)
Venous blood samples were collected for pharmacokinetic parameter estimates for LY404039 alone and in the presence of aqueous activated charcoal.
Time frame: Predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Population: Participants who received study drug(s), did not have an incidence of vomiting following administration of LY2140023, and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023 | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY404039 (Active Moiety) | 474 ng/mL | Geometric Coefficient of Variation 26 |
| 80 mg LY2140023 + 75 g Aqueous Activated Charcoal | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY404039 (Active Moiety) | 324 ng/mL | Geometric Coefficient of Variation 20 |