A Brain Imaging Study With Positron Emission Tomography a... | NCT02602860

Status Module

Name	Class
PRA Health Sciences	INDUSTRY
Yale University	OTHER

Oversight Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Levetiracetam	Experimental	Cohort 1: Half of the subjects will receive LEV as a 5 minute iv infusion during the second Positron Emission Tomography (PET) scan, 60 minutes after the start of [11C]UCB-J administration. Cohort 2: Half of the subjects will receive LEV as a 5 minute iv infusion during the first PET scan, 60 minutes after the start of [11C]UCB-J administration. The dose of LEV (500 mg to 2500 mg) or BRV (50 mg to 200 mg) will be decided based on the data obtained in Cohort 1. Subjects will return for a second PET imaging session (Visit 4), 7 to 28 days after completion of their first session (Visit 3) to enter the BRV arm.	Radiation: [11C]UCB-J Drug: Levetiracetam
Brivaracetam	Experimental	Cohort 1:Half of the subjects will receive BRV as a 5 minute iv infusion during the second Positron Emission Tomography (PET) scan, 60 minutes after the start of [11C]UCB-J administration. Cohort 2:Half of the subjects will receive BRV as a 5 minute iv infusion during the first PET scan, 60 minutes after the start of [11C]UCB-J administration. The dose of BRV (50-200 mg) will be decided based on the data obtained in Cohort 1. Subjects will return for a second PET imaging session,7 to 28 days after completion of their first session to enter the LEV arm. Cohort 3:void Cohort 4:Subjects will take oral BRV (25-100 mg bid) for 4 days and a single dose of BRV on Day 5. Pre-/post-block scans will be obtained at the first dose, one post-block scan after the last dose. Additional post-block scans may be obtained 8-10 and 28h or later after last dose; if last scan not needed, subject will return 7 to 28 days later for a post-block scan. Dose range for LEV in Cohort 4 will be 250 to <1500mg.	Radiation: [11C]UCB-J Drug: Brivaracetam

Interventions

Name	Type	Description	Arm Group Labels	Other Names
[11C]UCB-J	Radiation	Pharmaceutical form: Sterile solution for intravenous infusion Concentration: 20 mCi Route of Administration: iv	Brivaracetam Levetiracetam

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Level of synaptic vesicle glycoprotein 2A (SV2A) receptor occupancy during the displacement scans	The receptor occupancy will be determined using occupancy plots from the apparent volume of distribution, Vapp values.	Displacement scans (120 minutes)
Equilibrium tissue to plasma activity ratio (VT) of [11C]UCB-J	The equilibrium tissue to plasma activity ratio (VT) will be used to quantify [11C]UCB-J binding in each brain region of interest before and after administration of Brivaracetam and Levetiracetam.	Baseline (120 minutes) and Displacement scans (120 minutes)
Tracer displacement halftimes	Tracer displacement halftimes will be estimated from Displacement scans and Baseline scans on the average standardized uptake value (SUV) for all regions over time during 60-minute timeframe.	Baseline (120 minutes) and Displacement scans (120 minutes)
Tracer-exit corrected halftimes of Brivaracetam or Levetiracetam entry	Tracer-exit corrected halftimes of Brivaracetam or Levetiracetam entry will be estimated by subtracting the tracer clearance halftime from the displacement halftime.	Baseline (120 minutes) and Displacement scans (120 minutes)

Eligibility Module

Eligibility 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:

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

Name	Affiliation	Role
UCB Cares	+1-844-599-2273(UCB)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Ep0074 001		New Haven	Connecticut		United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30924924	Derived	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.

ID	Term
C000618323	1-((3-(methylpyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one
C482793	brivaracetam
D000077287	Levetiracetam

ID	Term
D000081	Acetamides
D000577	Amides
D009930	Organic Chemicals
D000085	Acetates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D011760	Pyrrolidinones
D011759	Pyrrolidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds