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

NCT03405714 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: EP00652016-002452-25
• Study Type: interventional
• Target: 50
• Locations: 7 countries
• Sites: 17

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.

Conditions

Epilepsy

Keywords

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

Outcome Measures

Primary Outcomes (29)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration - 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- 15 Minutes

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 3 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 3 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 3 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 3 (Day 1 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 4 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  At <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 4 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  At 15 minutes post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 4 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  At 3 hours post-initiation of iv BRV infusion at Visit 4 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Predose (<=1 Hour), Visit 5 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at <= 1 hour pre-initiation of intravenous (iv) BRV infusion at Visit 5 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 15 Minutes, Visit 5 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 15 minutes post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

• Plasma Concentration of Brivaracetam (BRV) at Postdose 3 Hours, Visit 5 by Infusion Duration- Bolus

  Blood samples were taken at indicated time points to determine brivaracetam (BRV) plasma concentration before, during, and after iv BRV administration.

  Blood samples were collected at 3 hours post-initiation of iv BRV infusion at Visit 5 (Day 2 of IV PK period)

• Number of Participants With Adverse Events (AEs)

  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.

  From Screening until last visit (up to Day 68)

• Number of Participant Withdrawals Due to Adverse Events

  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.

  From Screening until last visit (up to Day 68)

Study Arms (1)

Brivaracetam

EXPERIMENTAL

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

Interventions

Brivaracetam DRUG

* Pharmaceutical form: Solution for iv injection * Route of administration: intravenous use * Concentration: 10 mg/ml

Also known as: Briviact

Brivaracetam

Eligibility Criteria

• Age: 1 Month - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (17)

Ep0065 252

The Bronx, New York, 10467, United States

Location

Ep0065 237

Durham, North Carolina, 27710, United States

Location

Ep0065 502

Hradec Králové, Czechia

Location

Ep0065 240

Prague, Czechia

Location

Ep0065 242

Berlin, Germany

Location

Ep0065 254

Bielefeld, Germany

Location

Ep0065 210

Budapest, Hungary

Location

Ep0065 224

Budapest, Hungary

Location

Ep0065 247

Budapest, Hungary

Location

Ep0065 222

Debrecen, Hungary

Location

Ep0065 232

Miskolc, Hungary

Location

Ep0065 264

Milan, Italy

Location

Ep0065 238

Pavia, Italy

Location

Ep0065 239

Pavia, Italy

Location

Ep0065 230

Roma, Italy

Location

Ep0065 223

Aguas Calientes, Mexico

Location

Ep0065 248

Seville, Spain

Location

Related Publications (1)

• 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.

  PMID: 35196395 RESULT

Related Links

• Product Information
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Epilepsy

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

+1844 599

Study Officials

• UCB Cares

  001 844 599 2273 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 12, 2018
• First Posted: January 23, 2018
• Study Start: June 1, 2018
• Primary Completion: November 4, 2020
• Study Completion: November 4, 2020
• Last Updated: May 11, 2022
• Results First Posted: November 26, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1); IT (4); DE (2); CZ (2); US (2); HU (5); ES (1)