Clinical trial NCT03580707: Does BRV Have Faster Onset Time & Greater Effect Than LEV in Epilepsy Pts Using PPR Pharmacodynamic Efficacy Endpoint
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Photosensitive Epilepsy
Lead sponsor: Rosenfeld, William E., M.D.
Sponsor class: INDIV
Collaborators: name: Comprehensive Epilepsy Care Center for Children & Adults
name: Utrecht University
name: PRA Health Sciences
name: UCB Biopharma S.P.R.L.
First posted: 2018-07-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: "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)
timeFrame: Six weeks
Secondary outcomes:
measure: "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)
timeFrame: Six weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: The Comprehensive Epilepsy Care Center For Children And Adults
state: Missouri
Study officials:
affiliation: Comprehensive Epilepsy Care Center for Children & Adults
name: William E Rosenfeld, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reed RC, Rosenfeld WE, Lippmann SM, Eijkemans RMJC, Kasteleijn-Nolst Trenite DGA. Rapidity of CNS Effect on Photoparoxysmal Response for Brivaracetam vs. Levetiracetam: A Randomized, Double-blind, Crossover Trial in Photosensitive Epilepsy Patients. CNS Drugs. 2020 Oct;34(10):1075-1086. doi: 10.1007/s40263-020-00761-1.