Clinical trial NCT01591330: A Study of LY2140023 in Healthy Males and Females
Official title: A Particle Size Study of 3 Different Particle Size Test Tablet Formulations Compared to the Reference Tablet Formulation in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Denovo Biopharma LLC
Sponsor class: INDUSTRY
First posted: 2012-05-04
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY2140023
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Last Time Point of Measurable Concentration (AUC[0-tlast]) of LY2140023
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY404039 (Active Moiety)
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Last Time Point of Measurable Concentration (AUC[0-tlast]) of LY404039 (Active Moiety)
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Secondary outcomes:
measure: Pharmacokinetics: Time of Maximum Observed Drug Concentration (Tmax) of LY2140023
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Terminal Half Life (t1/2) of LY2140023
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Apparent Total Body Clearance (CL/F) of LY2140023
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Volume of Distribution During the Terminal Phase (Vz/F) of LY2140023
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Time of Maximum Observed Drug Concentrations (Tmax) of LY404039 (Active Moiety)
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Terminal Half Life (t1/2) of LY404039 (Active Moiety)
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Apparent Total Body Clearance (CL/F) of LY404039 (Active Moiety)
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
measure: Pharmacokinetics: Volume of Distribution During the Terminal Phase (Vz/F) of LY404039 (Active Moiety)
timeFrame: Predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16, and 24 hours postdose
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: 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.
state: West Yorkshire
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: