A Study of LY2140023 in Healthy Males and Females

Phase 1

Completed

Conditions: Healthy Volunteers

Interventions: Drug: LY2140023 Reference form
Drug: LY2140023 Test-Low
Drug: LY2140023 Test-Medium
Drug: LY2140023 Test-High

Registration Number: NCT01591330

Lead Sponsor: Denovo Biopharma LLC

Brief Summary: The study will evaluate the effect of different particle size of LY2140023. The study involves 4 single doses of 80 milligrams (mg) LY2140023 taken as 1 tablet by mouth with a washout period of at least 3 days between doses. This study will last approximately 60 days not including screening. Screening is required within 30 days prior to study entry.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

Inclusion Criteria

are overtly 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:
- female participants of child-bearing potential who test negative for pregnancy at screening and agree to use a reliable method of birth control for the duration of the study and for at least 3 months after the last dose of LY2140023
- female participants who are of non-childbearing potential (that is, postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy, or confirmed tubal occlusion [not tubal ligation]). Postmenopausal is defined as no menses for at least 1 year, or a plasma follicle stimulating hormone (FSH) value of >40 milli-international units per liter (mIU/mL), unless the participant is taking hormone replacement therapy
have a body mass index (BMI) of 19 to 32 kilograms per meter squared (kg/m^2), inclusive, at the time of screening
have clinical laboratory test results within normal reference ranges 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 chosen ethical review board (ERB)

Exclusion Criteria

are currently enrolled in or have completed or discontinued within the last 90 days from a clinical trial involving an investigational product, 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, LY404039, related compounds, or any components of the formulation
are persons who have previously completed or withdrawn from this study or any other study investigating LY2140023 and have previously received the investigational product
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 or pulse rate as determined by the investigator
have a history or presence of 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 evidence or any history of significant active neuropsychiatric disease
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)
- uncontrolled migraine or transient ischemic attack (TIA) within 1 year and/or 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 or without neurological deficits).
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
show evidence of human immunodeficiency (HIV) virus 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 with a positive pregnancy test or women who are lactating
intend to use over-the-counter (OTC) or prescription medication within 14 days prior to dosing of LY2140023
have donated blood of more than 500 milliliters (mL) within the 3 months prior to screening, or plan to donate blood within the 3 months after the last dose
have an average weekly alcohol intake that exceeds 28 units per week (males) and 21 units per week (females), or are unwilling to stop alcohol consumption for 48 hours prior to check-in for each treatment period until discharge in each period (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)
have a clinically significant abnormality in the neurological examination
participants judged prior to randomization to be at suicidal risk by the investigator
participants who are unwilling to refrain from tobacco- or nicotine-containing products while in the Clinical Research Unit (CRU) or are unable to abide by CRU restrictions
show evidence of pruritus or skin exfoliation
have an eosinophil count > 1.5 x 10^9 per liter (L)
show evidence of active renal disease or creatinine clearance (CrCl) less than 90 milliliters per minute (mL/min) (as calculated by the Cockcroft-Gault equation)
in the opinion of the investigator or sponsor, are unsuitable for inclusion in the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
LY2140023 Reference Form	LY2140023 Reference form	LY2140023: 80 mg, administered once, orally. There is a minimum 3-day washout period between dosing in one period and dosing in the next dosing period.
LY2140023 Test-Low	LY2140023 Test-Low	LY2140023: 80 mg, low particle size, administered once, orally. There is a minimum 3-day washout period between dosing in one period and dosing in the next dosing period.
LY2140023 Test-Medium	LY2140023 Test-Medium	LY2140023: 80 mg, medium particle size, administered once, orally. There is a minimum 3-day washout period between dosing in one period and dosing in the next dosing period.
LY2140023 Test-High	LY2140023 Test-High	LY2140023: 80 mg, high particle size, administered once, orally. There is a minimum 3-day washout period between dosing in one period and dosing in the next dosing period.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Last Time Point of Measurable Concentration (AUC[0-tlast]) of LY2140023	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Last Time Point of Measurable Concentration (AUC[0-tlast]) of LY404039 (Active Moiety)	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Maximum Concentration (Cmax) of LY2140023	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Maximum Concentration (Cmax) of LY404039 (Active Moiety)	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics: Time of Maximum Observed Drug Concentration (Tmax) of LY2140023	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Apparent Total Body Clearance (CL/F) of LY2140023	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Terminal Half Life (t1/2) of LY404039 (Active Moiety)	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Terminal Half Life (t1/2) of LY2140023	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Time of Maximum Observed Drug Concentrations (Tmax) of LY404039 (Active Moiety)	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Volume of Distribution During the Terminal Phase (Vz/F) of LY2140023	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Apparent Total Body Clearance (CL/F) of LY404039 (Active Moiety)	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Pharmacokinetics: Volume of Distribution During the Terminal Phase (Vz/F) of LY404039 (Active Moiety)	Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇬🇧
Leeds, West Yorkshire, United Kingdom
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇬🇧Leeds, West Yorkshire, United Kingdom