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

Rosenfeld, William E., M.D.

Status and phase: Completed; Phase 3; Phase 2

Conditions: Photosensitive Epilepsy

Treatments: Drug: BRV vs LEV in randomized double blinded, crossover fashion

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03580707

SAIRB-18-0016

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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16 participants in 2 patient groups

Part 1

Active Comparator group

Description:

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.

Treatment:

Drug: BRV vs LEV in randomized double blinded, crossover fashion

Part 2

Active Comparator group

Description:

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.

Treatment:

Drug: BRV vs LEV in randomized double blinded, crossover fashion