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

NCT ID: NCT02602860

Last Updated: 2017-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2017-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Healthy Volunteers

Keywords

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SV2A Levetiracetam Brivaracetam PET

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

[11C]UCB-J

Intervention Type RADIATION

* Pharmaceutical form: Sterile solution for intravenous infusion
* Concentration: 20 mCi
* Route of Administration: iv

Levetiracetam

Intervention Type DRUG

* Pharmaceutical form: Sterile solution for intravenous infusion
* Concentration: 100 mg/ml
* Route of Administration: iv

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.

Group Type EXPERIMENTAL

[11C]UCB-J

Intervention Type RADIATION

* Pharmaceutical form: Sterile solution for intravenous infusion
* Concentration: 20 mCi
* Route of Administration: iv

Brivaracetam

Intervention Type DRUG

* Pharmaceutical form: Sterile solution for intravenous infusion
* Concentration: 10 mg/ml
* Route of Administration: iv

Brivaracetam

Intervention Type DRUG

* Pharmaceutical form: Tablets for oral intake
* Concentration: 25 mg
* Route of Administration: oral

Interventions

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[11C]UCB-J

* Pharmaceutical form: Sterile solution for intravenous infusion
* Concentration: 20 mCi
* Route of Administration: iv

Intervention Type RADIATION

Brivaracetam

* Pharmaceutical form: Sterile solution for intravenous infusion
* Concentration: 10 mg/ml
* Route of Administration: iv

Intervention Type DRUG

Levetiracetam

* Pharmaceutical form: Sterile solution for intravenous infusion
* Concentration: 100 mg/ml
* Route of Administration: iv

Intervention Type DRUG

Brivaracetam

* Pharmaceutical form: Tablets for oral intake
* Concentration: 25 mg
* Route of Administration: oral

Intervention Type DRUG

Other Intervention Names

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[11C]APP311 UCB34714 Keppra L059 UCB34714

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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PRA Health Sciences

INDUSTRY

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role collaborator

UCB Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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UCB Cares

Role: STUDY_DIRECTOR

+1-844-599-2273(UCB)

Locations

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Ep0074 001

New Haven, Connecticut, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 30924924 (View on PubMed)

Other Identifiers

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EP0074

Identifier Type: -

Identifier Source: org_study_id