Clinical trial NCT01248052: A First Human Dose Study to Investigate Safety and Tolerability of LY2979165 in Healthy Volunteers
Official title: Single-Ascending Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of LY2979165 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bipolar Disorder
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-11-25
Enrollment: 25
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a two part study (Parts A and B), the purpose of which is to determine the safety of LY2979165 in healthy people, and any side effects that might be associated with it, and to understand how the body handles LY2979165. In addition, Part B, will also look at levels of LY2979165 in spinal fluid. Doses investigated will be in the range of 20-1000 mg.


Eligibility criteria: Inclusion Criteria:

* Are overtly healthy males or females, as determined by medical history and physical examination. Female subjects in Part B are at the site's discretion.
* Male subjects: Agree to use a reliable method of birth control during the study.
* Female subjects: Women not of child-bearing potential due to surgical sterilisation (hysterectomy or bilateral oophorectomy or tubal ligation) or postmenopausal as defined by age greater than or equal to 45 years with an intact uterus, who have not taken hormones or oral contraceptives for \> 1 year, and either:

  * spontaneous amenorrhea of \>12 months, or
  * spontaneous amenorrhea of 6-12 months with a follicle- stimulating hormone (FSH) level of \>40 mIU/mL
* Are between the body mass index (BMI) of 18.5 and 29.9 kg/m2, inclusive.
* 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 30 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/device 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.
* Are persons who have previously completed or withdrawn from this study.
* History of clinically significant adverse drug reactions or "drug allergy" to more than 3 different types of systemically administered medications or known allergies to LY2979165 or it's constituents.
* Have a Bazett's corrected QT (QTcB) interval value of \>450 msec (males) or \>470 msec (females) or any abnormality in the screening 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study.
* Have an abnormal blood pressure (at least 5 minutes in supine position) as determined by the investigator.
* Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, immunological, 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 increased risk of seizures as evidenced by a history of: greater than or equal to 1 seizure (except childhood febrile seizure), history of electroencephalogram with epileptiform activity, history of stroke, surgery to the cerebral cortex, or head trauma with loss of consciousness.
* Show evidence of significant active neuropsychiatric disease.
* Have a history of alcohol or drug abuse.
* Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies.
* Show evidence of hepatitis B and/or positive hepatitis B surface antigen.
* Have donated blood of more than 450 mL within the last 3 months prior to dosing.
* Intended use of over-the-counter medication within 7 days prior to dosing or during the study with the exception of vitamins and mineral supplements (not providing \>100% of the recommended dietary allowance \[RDA\]), or occasional paracetamol or acetaminophen. If this situation arises, inclusion of an otherwise suitable subject may be at the discretion of the sponsor.
* Intended use of herbal supplements or prescription medications, other than stable doses of thyroid or estrogen hormone replacement, within 14 days prior to dosing or during the study. If this situation arises, inclusion of an otherwise suitable subject may be at the discretion of the sponsor.
* Subjects who meet at least 1 of the following criteria (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits):

  * subjects who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females),
  * subjects unwilling to stop alcohol consumption 48 hours prior to dosing until the completion of each study appointment, or
  * subjects unwilling to limit alcohol intake to no more than 3 units per day between study appointments.
* Cigarette consumption of more than 10 cigarettes per day or unable/unwilling to abide by CRU smoking restrictions during admissions.
* Any other condition, which in the opinion of the investigator, would preclude participation in the study.

In addition for Part B only:

* Abnormalities in lumbar spine previously known or determined by screening lumbar x-ray.
* History of clinically significant back pain, back pathology and/or back injury (for example, degenerative disease, spinal deformity or spinal surgery) that may predispose to complications or technical difficulty with lumbar puncture.
* Have evidence or history of significant active bleeding or coagulation disorder or have taken non-steroidal anti inflammatory drugs (NSAIDs) or other drugs that affect coagulation or platelet function within 14 days prior to lumbar catheter insertion.
* Have an allergy to lidocaine (Xylocaine®) or its derivatives.
* Have medical or surgical conditions in which lumbar puncture is contraindicated.
* Have participated in Part A of this study.

Primary outcomes:
measure: Number of participants with clinically significant effects
timeFrame: predose through 48 hours postdose
Secondary outcomes:
measure: Pharmacokinetics, area under the concentration curve (AUC), Parts A and B
timeFrame: predose through 48 hours postdose
measure: Pharmacokinetics maximum plasma concentration (Cmax), Parts A and B.
timeFrame: predose through 48 hours post dose
measure: Pharmacokinetics, cerebrospinal fluid area under the concentration curve (AUC), Part B only
timeFrame: predose through 48 hours postdose
measure: Pharmacokinetics, maximum cerebrospinal fluid concentration (Cmax), Part B only
timeFrame: predose through 48 hours postdose
Other outcomes:
Locations:
city: Singapore
country: Singapore
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
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: