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

October 27, 2017 updated by: UCB Pharma

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States
        • Ep0074 001

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Levetiracetam

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
  • Pharmaceutical form: Sterile solution for intravenous infusion
  • Concentration: 20 mCi
  • Route of Administration: iv
Other Names:
  • [11C]APP311
Drug: Levetiracetam
  • Pharmaceutical form: Sterile solution for intravenous infusion
  • Concentration: 100 mg/ml
  • Route of Administration: iv
Other Names:
  • Keppra
  • L059
EXPERIMENTAL: Brivaracetam

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
  • Pharmaceutical form: Sterile solution for intravenous infusion
  • Concentration: 20 mCi
  • Route of Administration: iv
Other Names:
  • [11C]APP311
Drug: Brivaracetam
  • Pharmaceutical form: Sterile solution for intravenous infusion
  • Concentration: 10 mg/ml
  • Route of Administration: iv
Other Names:
  • UCB34714
Drug: Brivaracetam
  • Pharmaceutical form: Tablets for oral intake
  • Concentration: 25 mg
  • Route of Administration: oral
Other Names:
  • UCB34714

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of synaptic vesicle glycoprotein 2A (SV2A) receptor occupancy during the displacement scans
Time Frame: Displacement scans (120 minutes)
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
Time Frame: Baseline (120 minutes) and Displacement scans (120 minutes)
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
Time Frame: Baseline (120 minutes) and Displacement scans (120 minutes)
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
Time Frame: Baseline (120 minutes) and Displacement scans (120 minutes)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UCB Pharma

Collaborators

Yale University
PRA Health Sciences

Investigators

  • Study Director: UCB Cares, +1-844-599-2273(UCB)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 1, 2015

Primary Completion (ACTUAL)

September 1, 2017

Study Completion (ACTUAL)

September 1, 2017

Study Registration Dates

First Submitted

November 6, 2015

First Submitted That Met QC Criteria

November 9, 2015

First Posted (ESTIMATE)

November 11, 2015

Study Record Updates

Last Update Posted (ACTUAL)

October 30, 2017

Last Update Submitted That Met QC Criteria

October 27, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EP0074

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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