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Does BRV Have Faster Onset Time & Greater Effect Than LEV in Epilepsy Pts Using PPR Pharmacodynamic Efficacy Endpoint

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ClinicalTrials.gov Identifier: NCT03580707
Recruitment Status : Completed
First Posted : July 9, 2018
Last Update Posted : March 26, 2019
Sponsor:
Collaborators:
Comprehensive Epilepsy Care Center for Children & Adults
Utrecht University
PRA Health Sciences
UCB Biopharma S.P.R.L.
Information provided by (Responsible Party):
Rosenfeld, William E., M.D.

Brief Summary:
The main purpose of this study is to see whether brivaracetam has a faster onset time and greater effect than levetiracetam in subjects with photosensitive seizures. Part 1 of the study will compare the effects of levetiracetam 1500 mg with the effects of brivaracetam 100 mg. Part 2, will compare the effects of levetiracetam 1500 mg with the effects of brivaracetam 100 mg or will compare the effects of levetiracetam 500mg with the effects of brivaracetam 25 mg.

Condition or disease Intervention/treatment Phase
Photosensitive Epilepsy Drug: BRV vs LEV in randomized double blinded, crossover fashion Phase 2 Phase 3

Detailed Description:
The proposed study in epilepsy patients with photosensitivity intends to extend the animal findings for the faster (and perhaps greater) pharmacodynamic effect of intravenous BRV versus LEV at equipotent doses. Doses and infusion times were chosen based on proven safety profiles of both drugs (UCB, data on file): maximal dose of 1500 mg LEV in 15 minutes (or in 5 minutes) and 100 mg for BRV (15 times more potency of BRV compared to LEV). The study proposes a comparison of the rapidity of the CNS effects of both LEV and BRV within the same patient (randomized, two-way crossover, double-blind in a total 16 patients with epilepsy 8 patients in Part 1 and 8 patients in Part 2) Study Part 1: an IV infusion over 15 minutes, appropriately diluted (per package insert for LEV); BRV will also be administered as a 15-minute infusion (anticipating similar language in the package insert for BRV);Study Part 2, Option I: Assuming a statistically significant difference in the rapidity of CNS action has been observed from an analysis of the data set in Study Part 1, will proceed with Study Part 2 Option I. LEV or BRV will be administered, in a randomized, two-way crossover, double-blind design as an IV infusion over 5 minutes, appropriately diluted, to another cohort of 8 patients with photosensitive epilepsy. (Potentially, a few of the same patients as under 'a' above could participate herein, if they are willing to repeat the study). OR Study Part 2, Option II: Assuming no statistically significant difference in the rapidity of CNS action has been observed from an analysis of the data set in Study Part 1, will proceed with Study Part 2, Option II. LEV or BRV will be administered, in a randomized, two-way crossover, double-blind design as an IV infusion over again 15 minutes, appropriately diluted, to another cohort of 8 patients with photosensitive epilepsy. (Potentially, a few of the same patients as under 'a' above could participate herein, if they are willing to repeat the study). However, LEV will be given as a 500 mg dose, and BRV as a 25 mg dose. Use of lower, nearly equipotent minimally effective doses of LEV and BRV will maximize ability to readily differentiate the electroencephalographic PPR effect between the two AEDs.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Does BRV Have a Faster Onset Time and Greater Effect Than LEV in Epilepsy Patients?: A Prospective, Randomized, Crossover, Double-blind, Controlled Intravenous Study Using the PPR as a Pharmacodynamic Efficacy Endpoint
Actual Study Start Date : June 1, 2018
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : December 31, 2018


Arm Intervention/treatment
Active Comparator: Part 1
Compare rapidity of CNS effects of levetiracetam (LEV) & brivaracetam (BRV) within same pt-(randomized, two-way crossover, dbl-blind in total 16 pts w/epilepsy. Pt 1: IV infusion over 15 min BRV will also be administered as 15-min.infusion. BRV vs LEV in randomized double blinded, crossover fashion.
Drug: BRV vs LEV in randomized double blinded, crossover fashion
Single dose intravenous administration of BRV 100 mg over a 15 minutes period. On a subsequent occasion, (approximately 2 weeks later), the patient is crossed over to the other drug at a singular dose. On both occasions, intermittent photic stimulation is done 10 times in a two hour period. IPS is again conducted in the cross over portion as well. Coincident with IPS stimulation 10 blood samples will be drawn for BRV or LEV plasma concentration.
Other Name: Intermit pho stim respect over 2 hours/each of 2 study days

Active Comparator: Part 2
Pt 2 Op I:Assuming statistically signify. diff. in rapidity of CNS action has been observed from an analysis of data set in Pt 1,will proceed w/ Pt 2Opt I. Levetiracetam (LEV) or brivaracetam (BRV administered in randomized, two-way crossover, dbl-blind design as IV infusion over 5 min. to another cohort of 8 pts w/photosensitive epilepsy OR Pt 2,Opt II: Assuming no statistically signif. diff. in rapidity of CNS action has been observed from an analysis of data set in Pt 1, will proceed w/Pt 2,Opt II. LEV or BRV will be administered, in randomized, two-way crossover, dbl-blind design as IV infusion over again 15 min. to another cohort of 8 pts w/ photosensitive epilepsy. LEV will be given as 500 mg dose & BRV as 25 mg dose. BRV vs LEV in randomized double blinded, crossover fashion.
Drug: BRV vs LEV in randomized double blinded, crossover fashion
Single dose intravenous administration of BRV 100 mg over a 15 minutes period. On a subsequent occasion, (approximately 2 weeks later), the patient is crossed over to the other drug at a singular dose. On both occasions, intermittent photic stimulation is done 10 times in a two hour period. IPS is again conducted in the cross over portion as well. Coincident with IPS stimulation 10 blood samples will be drawn for BRV or LEV plasma concentration.
Other Name: Intermit pho stim respect over 2 hours/each of 2 study days




Primary Outcome Measures :
  1. "Comparison between Brivaracetam and Levetiracetam of the Time to Peak Effect (Abolition) and Time to >50% Diminution in Photo-Paroxysmal Response in Patients with Photosensitive Epilepsy" (1) [ Time Frame: Six weeks ]
    Difference in time (minutes) required between drugs, BRV& LEV to abolish a PPR (photo-paroxysmal response on the pts encephalogram, EEG) after intermittent photic stimulation (IPS) tested in the same pt of 2 separate occasions. In Pt 1, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion with 15-minute linear intravenous (i.v.) infusion of either 1500 mg LEV or BRV 100 mg as single dose. After 2 weeks, each pt will be tested in identical fashion w/opposite drug (crossover). Pt 2, Option 1, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Same single mg doses of LEV and BRV will be used, but i.v. infusion time will be 5 minutes;primary outcome measure will be same.Part 2, Option 2, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Single mg i.v. dose of 500 mg LEV or 25 mg BRV will be used, w/infusion time over 15 minutes;primary outcome measure will be the same.


Secondary Outcome Measures :
  1. "Comparison between Brivaracetam and Levetiracetam of the Time to Peak Effect (Abolition) and Time to >50% Diminution in Photo-Paroxysmal Response in Patients with Photosensitive Epilepsy" (2) [ Time Frame: Six weeks ]
    Difference in time (minutes) required between drugs,BRV & LEV to produce a >50% decrease in PPR (photo-paroxysmal response on pts encephalogram, EEG) after intermittent photic stimulation (IPS) tested in same pt of 2 separate occasions. Pt 1, 8 patients w/photosensitive epilepsy will be studied in double-blind, crossover fashion w/15-minute linear intravenous (i.v.) infusion of either 1500 mg LEV or BRV 100 mg as single dose. After 2 weeks, each pt will be tested in identical fashion w/opposite drug (crossover). In Pt 2, Option 1, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Same single mg doses of LEV and BRV will be used, but i.v. infusion time will be 5 minutes; primary outcome measure will be the same. Pt 2, Option 2, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Single mg i.v. dose of 500 mg LEV or 25 mg BRV will be used, with infusion time over 15 minutes; primary outcome measure will be same.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients between 18 and 65 years of age
  • Male or female
  • PPR at minimum at 60,50,40,30,25,20,18 or 16 Hz as upper threshold
  • Drug naïve or at most with up to 4 AEDs, not being LEV or BRV

Exclusion Criteria:

  • Current treatment with more than 4 AEDs
  • LEV or BRV as current treatment or used in the previous month.
  • History of severe side-effects or psychological side-effects with LEV or BRV use
  • Being pregnant or insufficiently protected against pregnancy (see also ref 31) or lactating Female
  • Serious internal medical disease (renal/hepatic/cardiovascular disease) as deemed by the on-site physician (WER)
  • History of psychiatric disease that has been a reason for acute hospitalisation for their condition of depression, schizophrenia, mania, delirium or aggressive behaviour
  • History of status epilepticus
  • History of significant ethanol or illicit drug use

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03580707


Locations
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United States, Missouri
The Comprehensive Epilepsy Care Center For Children And Adults
Saint Louis, Missouri, United States, 63141
Sponsors and Collaborators
Rosenfeld, William E., M.D.
Comprehensive Epilepsy Care Center for Children & Adults
Utrecht University
PRA Health Sciences
UCB Biopharma S.P.R.L.
Investigators
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Principal Investigator: William E Rosenfeld, M.D. Comprehensive Epilepsy Care Center for Children & Adults

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Responsible Party: Rosenfeld, William E., M.D.
ClinicalTrials.gov Identifier: NCT03580707     History of Changes
Other Study ID Numbers: SAIRB-18-0016
First Posted: July 9, 2018    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Epilepsy
Epilepsy, Reflex
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases