Healthy VolunteersPhase 1NCT02602860
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
A Phase 1 study testing [11C]UCB-J, Brivaracetam and Levetiracetam in people with Healthy Volunteers, run by UCB Pharma at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- [11C]UCB-J, Brivaracetam and Levetiracetam
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Healthy Volunteers
- Being tested
- [11C]UCB-J, Brivaracetam, Levetiracetam
- Keywords
- SV2A, Levetiracetam, Brivaracetam, PET
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[11C]UCB-JRadiation
Also called [11C]APP311
- Pharmaceutical form: Sterile solution for intravenous infusion
- Concentration: 20 mCi
- Route of Administration: iv
BrivaracetamDrug
Also called UCB34714
- Pharmaceutical form: Sterile solution for intravenous infusion
- Concentration: 10 mg/ml
- Route of Administration: iv
LevetiracetamDrug
Also called Keppra, L059
- Pharmaceutical form: Sterile solution for intravenous infusion
- Concentration: 100 mg/ml
- Route of Administration: iv
BrivaracetamDrug
Also called UCB34714
- Pharmaceutical form: Tablets for oral intake
- Concentration: 25 mg
- Route of Administration: oral
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Radiation: [11C]UCB-J; Drug: Brivaracetam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (120 minutes) and Displacement scans (120 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2015 (estimated)
- Study startNov 2015
- Primary completionSep 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences, Yale University
- Responsible party
- Sponsor
- Investigators
- UCB Cares, Study director, +1-844-599-2273(UCB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02602860
- Sponsor's protocol ID
- EP0074
- Status last verified
- Oct 2017
- First submitted
- 6 Nov 2015
- Last updated
- 30 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30924924
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02602860
- Acronym / sponsor ID
- EP0074
- Conditions
- Healthy Volunteers
- Keywords
- SV2A, Levetiracetam, Brivaracetam, PET
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- UCB PharmaIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences, Yale University
- Study start
- Nov 2015 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 11 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levetiracetam | Experimental | Radiation: [11C]UCB-J, Drug: LevetiracetamCohort 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. |
| Brivaracetam | Experimental | Radiation: [11C]UCB-J, Drug: BrivaracetamCohort 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [11C]UCB-JAlso: [11C]APP311* Pharmaceutical form: Sterile solution for intravenous infusion * Concentration: 20 mCi * Route of Administration: iv | Radiation | Brivaracetam, Levetiracetam |
| BrivaracetamAlso: UCB34714* Pharmaceutical form: Sterile solution for intravenous infusion * Concentration: 10 mg/ml * Route of Administration: iv | Drug | Brivaracetam |
| LevetiracetamAlso: Keppra, L059* Pharmaceutical form: Sterile solution for intravenous infusion * Concentration: 100 mg/ml * Route of Administration: iv | Drug | Levetiracetam |
| BrivaracetamAlso: UCB34714* Pharmaceutical form: Tablets for oral intake * Concentration: 25 mg * Route of Administration: oral | Drug | Brivaracetam |
Primary outcome
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.
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2017.
- Derived from this study: PubMed 30924924Finnema 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UCB Cares study director
+1-844-599-2273(UCB)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [11C]UCB-J, Brivaracetam and Levetiracetam in people with Healthy Volunteers, run by UCB Pharma at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Level of synaptic vesicle glycoprotein 2A (SV2A) receptor occupancy during the displacement scans (time frame: Displacement scans (120 minutes)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02602860, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2017.