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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02602860
• Other study ID #: EP0074
• Status: Completed
• Phase: Phase 1
• First received: November 6, 2015
• Last updated: October 27, 2017
• Start date: November 2015
• Est. completion date: September 2017

Study information

• Verified date: October 2017
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Radiation:
• [11C]UCB-J
Pharmaceutical form: Sterile solution for intravenous infusion Concentration: 20 mCi Route of Administration: iv

Drug:
• Brivaracetam
Pharmaceutical form: Sterile solution for intravenous infusion Concentration: 10 mg/ml Route of Administration: iv
• Levetiracetam
Pharmaceutical form: Sterile solution for intravenous infusion Concentration: 100 mg/ml Route of Administration: iv
• Brivaracetam
Pharmaceutical form: Tablets for oral intake Concentration: 25 mg Route of Administration: oral

Locations

Country	Name	City	State
United States	Ep0074 001	New Haven	Connecticut

Sponsors (3)

Lead Sponsor	Collaborator
UCB Pharma	PRA Health Sciences, Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)