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

NCT03580707 | Completed Phase 2 FDA Drug

• 1 other identifier: SAIRB-18-0016
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Photosensitive Epilepsy

Outcome Measures

Primary Outcomes (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)

  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.

  Six weeks

Secondary Outcomes (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)

  Six weeks

Study Arms (2)

Part 1

ACTIVE COMPARATOR

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

Part 2

ACTIVE COMPARATOR

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

Interventions

BRV vs LEV in randomized double blinded, crossover fashion DRUG

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.

Also known as: Intermit pho stim respect over 2 hours/each of 2 study days

Part 1; Part 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rosenfeld, William E., M.D.: lead
• Comprehensive Epilepsy Care Center for Children & Adults: collaborator
• Utrecht University: collaborator
• PRA Health Sciences: collaborator
• UCB Biopharma S.P.R.L.: collaborator

Study Sites (1)

The Comprehensive Epilepsy Care Center For Children And Adults

St Louis, Missouri, 63141, United States

Location

Related Publications (1)

• 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.

  PMID: 32949370 DERIVED

MeSH Terms

Conditions

Epilepsy, Reflex

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• William E Rosenfeld, M.D.

  Comprehensive Epilepsy Care Center for Children & Adults

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: July 9, 2018
• Study Start: June 1, 2018
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: March 26, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)