Healthy Participants
Conditions
Brief summary
The purpose of this study is to assess the extent and rate of absorption of LY2140023 in healthy participants. The study has two periods. In Treatment Period 1, participants will receive a single oral dose of 80 milligrams (mg) LY2140023 followed by a 2-hour intravenous (IV) infusion of approximately 100 micrograms (µg) LY2140023 containing approximately 100 nanocuries (nCi) \[14C\]-LY2140023. In Treatment Period 2, participants will receive an oral dose of 80 mg LY2140023 followed by a 2-hour IV infusion of approximately 100 µg LY404039 containing approximately 100 nCi \[14C\]-LY404039. There will be at least a 3-day washout between doses.
Interventions
Sponsors
Denovo Biopharma LLC
Study design
Allocation
NON_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 healthy males or females of non-childbearing potential, as determined by medical history and physical examination * Male participants: must 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 non-childbearing potential i.e. 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 million international units/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) * Have venous access sufficient to allow for intravenous infusion and blood sampling
Exclusion criteria
* Are currently enrolled in or 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 participated in any clinical trial involving a radiolabeled investigational product or been exposed to radiolabeled substances (for treatment or diagnosis) within the last 12 months * Have known allergies to LY2140023 or LY404039, related compounds, or any components of the formulation * Are persons 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 \[lacking focality, lasting less than 15 minutes, and not associated with a central nervous system (CNS) infection or severe metabolic disturbance\] 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 a 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 80 milliliters/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: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1 | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16 and 24 hours postdose | Exposure of LY2140023 (parent compound), LY404039 (active metabolite), 14C-radiolabeled LY2140023, and 14C-radiolabeled LY404039 in terms of Area Under the Concentration Versus Time Curve from time 0 extrapolated to infinity (AUC\[0-inf\]) is summarized for participants in Treatment Period 1. |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 2 | Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16 and 24 hours postdose | Exposure of LY2140023 (parent compound), LY404039 (active metabolite), and 14C-radiolabeled LY404039 in terms of Area Under the Concentration Versus Time Curve from time 0 extrapolated to infinity (AUC\[0-inf\]) is summarized for participants in Treatment Period 2. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral 80 mg LY2140023 on Two Separate Occasions Participants received a single oral dose of 80 mg LY2140023 (parent compound) on 2 separate occasions.
In Treatment Period 1, a single oral dose of 80 mg LY2140023 followed by a single 2-hour IV infusion of approximately 100 µg LY2140023 containing approximately 100 nCi \[14C\]-LY2140023.
In Treatment Period 2, a single oral dose of 80 mg LY2140023 followed by a single 2-hour IV infusion of approximately 100 µg LY404039 (active metabolite) containing approximately 100 nCi \[14C\]-LY404039.
There was a washout period of at least 3 days between Treatment Period 1 and Treatment Period 2. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Washout Period (at Least 3 Days) | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Oral 80 mg LY2140023 on Two Separate Occasions |
|---|---|
| Age, Continuous | 34.2 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 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 | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 18 Participants |
| Region of Enrollment United Kingdom | 18 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 18 | 10 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1
Exposure of LY2140023 (parent compound), LY404039 (active metabolite), 14C-radiolabeled LY2140023, and 14C-radiolabeled LY404039 in terms of Area Under the Concentration Versus Time Curve from time 0 extrapolated to infinity (AUC\[0-inf\]) is summarized for participants in Treatment Period 1.
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16 and 24 hours postdose
Population: Participants who received oral LY2140023 with IV \[14C\]-LY2140023 and had evaluable pharmacokinetic (PK) concentration data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1 | LY2140023 (parent compound) | 1160 nanograms times hours per milliliter | Geometric Coefficient of Variation 28 |
| Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1 | LY404039 (active metabolite) | 2620 nanograms times hours per milliliter | Geometric Coefficient of Variation 23 |
| Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1 | [14C]-LY2140023 (parent) | 2.01 nanograms times hours per milliliter | Geometric Coefficient of Variation 22 |
| Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1 | [14C]-LY404039 (active metabolite) | 6.19 nanograms times hours per milliliter | Geometric Coefficient of Variation 20 |
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 2
Exposure of LY2140023 (parent compound), LY404039 (active metabolite), and 14C-radiolabeled LY404039 in terms of Area Under the Concentration Versus Time Curve from time 0 extrapolated to infinity (AUC\[0-inf\]) is summarized for participants in Treatment Period 2.
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16 and 24 hours postdose
Population: Participants who received oral LY2140023 with IV \[14C\]-LY404039 and had evaluable PK concentration data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 2 | LY2140023 (parent compound) | 1200 nanograms times hours per milliliter | Geometric Coefficient of Variation 27 |
| Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 2 | LY404039 (active metabolite) | 2690 nanograms times hours per milliliter | Geometric Coefficient of Variation 21 |
| Oral 80 mg LY2140023 and IV LY2140023/[14C]-LY2140023 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 2 | [14C]-LY404039 (active metabolite) | 7.69 nanograms times hours per milliliter | Geometric Coefficient of Variation 20 |