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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.

Tracking Information
First Submitted Date  ICMJE May 24, 2018
First Posted Date  ICMJE July 9, 2018
Last Update Posted Date March 26, 2019
Actual Study Start Date  ICMJE June 1, 2018
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2018)
"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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03580707 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2018)
"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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Does BRV Have Faster Onset Time & Greater Effect Than LEV in Epilepsy Pts Using PPR Pharmacodynamic Efficacy Endpoint
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Photosensitive Epilepsy
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: BRV vs LEV in randomized double blinded, crossover fashion
  • 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.
    Intervention: Drug: BRV vs LEV in randomized double blinded, crossover fashion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 25, 2018)
16
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 31, 2018
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03580707
Other Study ID Numbers  ICMJE SAIRB-18-0016
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rosenfeld, William E., M.D.
Study Sponsor  ICMJE Rosenfeld, William E., M.D.
Collaborators  ICMJE
  • Comprehensive Epilepsy Care Center for Children & Adults
  • Utrecht University
  • PRA Health Sciences
  • UCB Biopharma S.P.R.L.
Investigators  ICMJE
Principal Investigator: William E Rosenfeld, M.D. Comprehensive Epilepsy Care Center for Children & Adults
PRS Account Rosenfeld, William E., M.D.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP