Clinical trial NCT02602860: A Brain Imaging Study With Positron Emission Tomography and the Radiotracer [11C]UCB-J to Estimate How Fast Brivaracetam and Levetiracetam Enter the Brain in Healthy Volunteers
Official title: A Single-center, Open-label Positron Emission Tomography Study to Evaluate the Time-course of Displacement of [11C]UCB-J by Brivaracetam and Levetiracetam in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: SV2A
Levetiracetam
Brivaracetam
PET
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
name: Yale University
First posted: 2015-11-11
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This study will estimate how fast two antiepileptic drugs (Levetiracetam and Brivaracetam) enter the human brain. Brain imaging will be used to measure how quickly the radioactive probe \[11C\]UCB-J exits the brain when Levetiracetam or Brivaracetam are given. This will be used to estimate how fast the antiepileptic drugs enter the brain.


Eligibility criteria: Inclusion Criteria:

Inclusion Criteria:

* Subject is male or female and between 18 to 55 years of age (inclusive)
* Subject is in good physical and mental health, in the opinion of the Investigator, determined on the basis of medical history, physical and neurological examinations, vital signs, 12-lead Electrocardiography (ECG), and clinical laboratory tests
* Female subjects of childbearing potential must have a negative pregnancy test; female subjects of childbearing potential have to confirm that, for 1 month prior to the first administration of the study medication and during the entire study until the Safety Follow-Up (SFU) Visit she will either use a highly effective contraceptive method (eg, oral contraception, intrauterine device, diaphragm with spermicide) or abstain from sexual activity that can cause pregnancy

Exclusion Criteria:

Exclusion Criteria:

* History or presence of clinically significant respiratory, gastrointestinal, renal, hepatic, pancreatic, hematological, cardiovascular, musculoskeletal, genitourinary, immunological, or dermatological disorders, or any type of cancer
* Subject has a history of a neurological diagnosis, including but not limited to stroke, traumatic brain injury, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, or any other neurological disorder that may influence the outcome or analysis of the scan results
* History of donation of more than 450 mL of blood within 60 days prior to dosing in the Yale PET center or planned donation before 30 days has elapsed since intake of study drug
* The subject has Magnetic Resonance Imaging -incompatible (MRI - incompatible) implants and other contraindications for MRI, such as a pacemaker, artificial joints, non-removable body piercings, etc.
* Subjects who have received a diagnostic or therapeutic radiopharmaceutical less than 7 days prior to participation in this study
* Participation in other recent research studies \< 1 month or \< 1 year for studies involving ionizing radiation that would cause the subject to exceed the yearly dose limits for healthy volunteers

Primary outcomes:
measure: Level of synaptic vesicle glycoprotein 2A (SV2A) receptor occupancy during the displacement scans
timeFrame: Displacement scans (120 minutes)
measure: Equilibrium tissue to plasma activity ratio (VT) of [11C]UCB-J
timeFrame: Baseline (120 minutes) and Displacement scans (120 minutes)
measure: Tracer displacement halftimes
timeFrame: Baseline (120 minutes) and Displacement scans (120 minutes)
measure: Tracer-exit corrected halftimes of Brivaracetam or Levetiracetam entry
timeFrame: Baseline (120 minutes) and Displacement scans (120 minutes)
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Ep0074 001
state: Connecticut
Study officials:
affiliation: +1-844-599-2273(UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: Finnema SJ, Rossano S, Naganawa M, Henry S, Gao H, Pracitto R, Maguire RP, Mercier J, Kervyn S, Nicolas JM, Klitgaard H, DeBruyn S, Otoul C, Martin P, Muglia P, Matuskey D, Nabulsi NB, Huang Y, Kaminski RM, Hannestad J, Stockis A, Carson RE. A single-center, open-label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers. Epilepsia. 2019 May;60(5):958-967. doi: 10.1111/epi.14701. Epub 2019 Mar 29.