A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Intravenous Brivaracetam in Subjects >= 1 Month to < 16 Years of Age With Epilepsy

• ClinicalTrials.gov Identifier: NCT03405714
• Recruitment Status: Completed
• First Posted: January 23, 2018
• Results First Posted: November 26, 2021
• Last Update Posted: May 11, 2022
• Sponsor: UCB Biopharma S.P.R.L.
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma S.P.R.L. )

Study Description

Brief Summary:

The purpose of the study is to evaluate the pharmacokinetics (PK), safety, and tolerability of brivaracetam (BRV) administered intravenously (iv) in subjects >= 1 month to < 16 years of age with epilepsy.

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: Brivaracetam	Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Intravenous Brivaracetam in Subjects >= 1 Month < 16 Years of Age With Epilepsy
• Actual Study Start Date: June 1, 2018
• Actual Primary Completion Date: November 4, 2020
• Actual Study Completion Date: November 4, 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Brivaracetam; Brivaracetam will be administered to various age-based cohorts. Cohort 1: Subjects >=12 to <16 years; Cohort 2: Subjects >=6 to <12 years; Cohort 3: Subjects >=2 to <6 years; Cohort 4: Subjects 1 month to <2 years. Enrollment will be sequential by descending age beginning with Cohort 1. For each cohort, the first half will receive a 15-minute iv infusion. The Data Monitoring Committee (DMC) will then review safety and, as available, PK data to make the following recommendations: the progression of the current cohort (up to 2-minute iv bolus infusion) and progression to initiate enrollment in the preceding cohort.

Drug: Brivaracetam; Pharmaceutical form: Solution for iv injection; Route of administration: intravenous use; Concentration: 10 mg/ml; Other Name: Briviact

Outcome Measures

Primary Outcome Measures :

1. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 [ Time Frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
2. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 [ Time Frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
3. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 [ Time Frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
4. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 [ Time Frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
5. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 [ Time Frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
6. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 [ Time Frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
7. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 [ Time Frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
8. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 [ Time Frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
9. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 [ Time Frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) ]
   Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
10. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration - 15 Minutes [ Time Frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
11. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- 15 Minutes [ Time Frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
12. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- 15 Minutes [ Time Frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
13. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- 15 Minutes [ Time Frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
14. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- 15 Minutes [ Time Frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
15. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- 15 Minutes [ Time Frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
16. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- 15 Minutes [ Time Frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
17. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- 15 Minutes [ Time Frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
18. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- 15 Minutes [ Time Frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
19. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration- Bolus [ Time Frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
20. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- Bolus [ Time Frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
21. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- Bolus [ Time Frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
22. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- Bolus [ Time Frame: At <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
23. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- Bolus [ Time Frame: At 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
24. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- Bolus [ Time Frame: At 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
25. Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- Bolus [ Time Frame: Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
26. Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- Bolus [ Time Frame: Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
27. Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- Bolus [ Time Frame: Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period) ]
    Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.
28. Number of Participants With Adverse Events (AEs) [ Time Frame: From Screening until last visit (up to Day 68) ]
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
29. Number of Participant Withdrawals Due to Adverse Events [ Time Frame: From Screening until last visit (up to Day 68) ]
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female from >= 1 month to < 16 years of age. For subjects who are < 1 year from birth and who were preterm infants, the corrected gestational age should be used for this entry requirement
• Weight >= 3 kg (6.6 lbs)
• Diagnosis of epilepsy
• Acceptable candidate for venipuncture and intravenous (iv) infusion
• Treatment with >=1 anti epileptic drug (AED; including BRV) without a change of dose regimen for at least 7 days prior to Screening
• No treatment with vagus nerve stimulation (VNS), OR the subject is being treated with VNS and the settings have been constant for >=7 days prior to Screening
• For female subjects: not of childbearing potential, OR of childbearing potential and not sexually active/negative pregnancy test, OR of childbearing potential and sexually active/negative pregnancy test/uses medically acceptable contraceptive methods

Exclusion Criteria:

• Subject has previously received iv Brivaracetam (BRV) in this study
• Subject is being treated with BRV at a dose >5mg/kg/day (rounded) or >200mg/day for subjects with body weights >40kg
• Subject requires or is likely to require a change in concomitant antiepileptic drug(s) (AED[s]), dose of concomitant AED(s), or formulation of AED(s) during the 7 days prior to the intravenous (iv) pharmacokinetic (PK) Period
• Subject is likely, in the opinion of the Investigator, to require rescue medication during the Initiating Oral BRV (IOB) Treatment or iv PK Periods
• Subject has experienced generalized convulsive status epilepticus in the 28 days prior to Screening or during the Screening Period

Contacts and Locations

Locations

United States, New York

Ep0065 252

Bronx, New York, United States, 10467

United States, North Carolina

Ep0065 237

Durham, North Carolina, United States, 27710

Czechia

Ep0065 502

Hradec Králové, Czechia

Ep0065 240

Praha 4, Czechia

Germany

Ep0065 242

Berlin, Germany

Ep0065 254

Bielefeld, Germany

Hungary

Ep0065 210

Budapest, Hungary

Ep0065 224

Budapest, Hungary

Ep0065 247

Budapest, Hungary

Ep0065 222

Debrecen, Hungary

Ep0065 232

Miskolc, Hungary

Italy

Ep0065 264

Milan, Italy

Ep0065 238

Pavia, Italy

Ep0065 239

Pavia, Italy

Ep0065 230

Roma, Italy

Mexico

Ep0065 223

Aguas Calientes, Mexico

Spain

Ep0065 248

Sevilla, Spain

Sponsors and Collaborators

UCB Biopharma S.P.R.L.

Investigators

• Study Director: UCB Cares; 001 844 599 2273 (UCB)

  Study Documents (Full-Text)

Documents provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):

Study Protocol  [PDF] June 19, 2019

Statistical Analysis Plan  [PDF] September 25, 2020

More Information

Additional Information:

Product Information 

FDA Safety Alerts and Recalls 

Publications of Results:

Farkas MK, Kang H, Fogarasi A, Bozorg A, James GD, Krauwinkel W, Morita D, Will E, Elshoff JP. Pharmacokinetics, safety, and tolerability of intravenous brivaracetam in pediatric patients with epilepsy: An open-label trial. Epilepsia. 2022 Apr;63(4):855-864. doi: 10.1111/epi.17187. Epub 2022 Feb 23.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT03405714
• Other Study ID Numbers: EP0065; 2016-002452-25 ( EudraCT Number )
• First Posted: January 23, 2018
• Results First Posted: November 26, 2021
• Last Update Posted: May 11, 2022
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):

Epilepsy; Brivaracetam; Briviact; Open-label; pediatric; intravenous

Additional relevant MeSH terms:

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brivaracetam; Anticonvulsants