Clinical trial NCT01389596: A Study of the Efficacy and Safety of Pregabalin as Add-On Therapy for Partial Onset Seizures in Children Ages 4-16 Years
Official title: A DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER STUDY OF THE EFFICACY AND SAFETY OF PREGABALIN AS ADJUNCTIVE THERAPY IN CHILDREN 4 -16 YEARS OF AGE WITH PARTIAL ONSET SEIZURES
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy, Partial Seizures
Keywords: safety
efficacy
partial onset seizures
pediatric
pregabalin
placebo-controlled
double-blind
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-07-08
Enrollment: 295
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study A0081041 is a double blind, placebo controlled, randomized, parallel group, multicenter study to evaluate the safety and efficacy of two dose levels of pregabalin administered in equally divided daily doses, in either capsule or oral liquid formulation, as adjunctive therapy in pediatric subjects 4 to 16 years of age with partial onset seizures.


Eligibility criteria: Inclusion Criteria:

* Subjects and/or parent(s)/legally acceptable representative must be considered willing and able to sign consent, and complete daily seizure diaries and monitor seizure frequency.
* Male and female epilepsy subjects, 4 to 16 years of age inclusive on the date of the Screening Visit.
* Diagnosis of epilepsy with partial onset seizures classified as simple partial, complex partial or partial becoming secondarily generalized, according to the International League Against Epilepsy (ILAE) Diagnosis criteria.
* Must have a partial onset seizure frequency of at least 3 seizures per 28 day period prior to screening. Must have a partial onset seizure frequency of at least 6 seizures and no continuous 4 week seizure free period during the 8 week baseline phase prior to randomization.
* Currently receiving a stable dose of 1 to 3 antiepileptic drugs (stable within 28 days prior to screening).

Exclusion Criteria:

* Primary generalized seizures (including in the setting of co-existing partial onset seizures) which include, for example: Clonic, tonic and clonic-tonic seizures (note that partial onset seizures that become secondarily generalized are not exclusionary); Absence seizures; Infantile spasms; Myoclonic, myoclonic atonic, myoclonic tonic seizures.
* Lennox Gastaut syndrome, Benign Epilepsy with Centrotemporal Spikes (BECTS) and Dravet syndrome.
* A current diagnosis of febrile seizures, or seizures related to an ongoing acute medical illness. Any febrile seizures within 1 year of screening.
* Status epilepticus within 1 year prior to screening.
* Seizures related to drugs, alcohol, or acute medical illness.
* Any change in AED regimen (type of medication or dose) within 28 days of the Screening Visit or during the Baseline Phase.
* Progressive structural CNS lesion or a progressive encephalopathy.

Primary outcomes:
measure: Log-Transformed 28-Day Seizure Rate For All Partial Onset Seizures During Baseline Phase
timeFrame: Baseline phase (up to 8 weeks prior to treatment phase [Day 1])
measure: Log-Transformed 28-Day Seizure Rate For All Partial Onset Seizures During 12-Week Treatment Phase
timeFrame: Day 1 up to Week 12
Secondary outcomes:
measure: Percentage of Participants With at Least 50 Percent (%) or Greater Reduction From Baseline in 28-day Seizure Rate During the 12 Week Treatment Phase
timeFrame: Day 1 up to Week 12
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to 7 days after last dose of study drug (up to 13 weeks)
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to 7 days after last dose of study drug (up to 13 weeks)
measure: Number of Adverse Events by Severity
timeFrame: Day 1 up to 7 days after last dose of study drug (up to 13 weeks)
measure: Number of Participants (6-16 Years of Age) With Positive Response to Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories At Baseline
timeFrame: Baseline (4 week prior to Day 1 of treatment)
measure: Number of Participants (6-16 Years of Age) With Positive Response to Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories During Post Baseline Time Period
timeFrame: Day 1 up to Week 13
measure: Child Behaviour Checklist (CBCL): Internalizing Subscale Score in Participants Less Than 6 Years of Age
timeFrame: Week -8 (8 weeks prior to Day 1 of treatment), Week -4 (4 weeks prior to Day 1 of treatment), Day 1 (Week 0), Week 1, 2, 3, 6, 9, 12, end of study visit (Week 13)
measure: Child Behaviour Checklist (CBCL): Withdrawn Subscale Score in Participants Less Than 6 Years of Age
timeFrame: Week -8 (8 weeks prior to Day 1 of treatment), Week -4 (4 weeks prior to Day 1 of treatment), Day 1 (Week 0), Week 1, 2, 3, 6, 9, 12, end of study visit (Week 13)
measure: Child Behaviour Checklist (CBCL): Total Problem Subscale Score in Participants Less Than 6 Years of Age
timeFrame: Week -8 (8 weeks prior to Day 1 of treatment), Week -4 (4 weeks prior to Day 1 of treatment), Day 1 (Week 0), Week 1, 2, 3, 6, 9, 12, end of study visit (Week 13)
measure: Change From Baseline in Cognitive Test Battery (CogState Battery) Scores at Week 12: Detection Task
timeFrame: Baseline (pre-dose at Day 1), Week 12
measure: Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Week 12: Paediatric Identification (Go-No Go: Attention) Tasks
timeFrame: Baseline (pre-dose at Day 1), Week 12
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline (from 8 weeks prior to Day 1 of treatment) up to Week 13
measure: Number of Participants With Vital Signs Abnormalities
timeFrame: Baseline (from 8 weeks prior to Day 1 of treatment) up to Week 13
measure: Number of Participants With Clinically Significant Change From Baseline in Neurological Examinations
timeFrame: Baseline (from 8 weeks prior to Day 1 of treatment) up to Week 13
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline (from 8 weeks prior to Day 1 of treatment) up to Week 13
measure: Number of Participants With Clinically Significant Change From Baseline in Physical Examinations at Week 13
timeFrame: Baseline (from 8 weeks prior to Day 1 of treatment) up to Week 13
Locations:
city: Tucson
country: United States
facility: Center for Neurosciences
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Children´s Hospital Los Angeles
state: California
city: Loxahatchee Groves
country: United States
facility: Axcess Medical Research
state: Florida
city: North Palm Beach
country: United States
facility: Laszlo J. Mate, M.D., P.A.
state: Florida
city: Orlando
country: United States
facility: Pediatric Neurology, P.A.
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Neurological Clinic
state: Florida
city: Lexington
country: United States
facility: Center for Clinical and Translational Science
state: Kentucky
city: Lexington
country: United States
facility: Kentucky Neuroscience Institute
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Hospital Epilepsy Monitoring Unit
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Hospital Pharmacy, UK Chandler Hosptial
state: Kentucky
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical
state: Kentucky
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Physicians
state: Kentucky
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: Durham
country: United States
facility: Duke Children's Hospital and Health Center
state: North Carolina
city: Durham
country: United States
facility: Duke Clinical Research Unit
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: San Antonio
country: United States
facility: Road Runner Research, Ltd.
state: Texas
city: Ottignies
country: Belgium
facility: Centre Hospitalier Neurologique William Lennox
state: Brabant Wallon
city: Brussels
country: Belgium
facility: HUDERF
state: Brussels-capital
city: Brussels
country: Belgium
facility: Cliniques Universitaires de Bruxelles Hôpital Erasme
city: Plovdiv
country: Bulgaria
facility: UMBAL Sveti Georgi, Klinika po pediatria i genetichni zabolyavania
city: Brno - Cerna Pole
country: Czechia
facility: Fakultni nemocnice Brno - Detska nemocnice
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Bordeaux
country: France
facility: CHU Bordeaux - Hopital des Enfants
city: Bron
country: France
facility: Hôpital Mère Enfant
city: Garches
country: France
facility: Hopital Raymond Poincare
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg - Hopital Hautepierre
city: Athens
country: Greece
facility: General Childrens Hospital of Athens P & A Kyriakou
city: Athens
country: Greece
facility: General Children's Hospital Penteli
city: Balassagyarmat
country: Hungary
facility: Dr. Kenessey Albert Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak Budai Egyesitett Korhazak
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, I. Sz. Gyermekgyogyaszati Klinika
city: Budapest
country: Hungary
facility: Heim Pal Gyermekkorhaz, Neurologiai Osztaly
city: Budapest
country: Hungary
facility: Magyarorszagi Reformatus Egyhaz Bethesda Gyermekkorhaz, Gyermekneurologia
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Ancona
country: Italy
facility: A.O.U. Ospedali Riuniti di Ancona Presidio Ospedaliero G. Salesi
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Meyer
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Nazionale Casimiro Mondino, IRCCS - Servizio di Farmacia
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Nazionale Casimiro Mondino, IRCCS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center/ Department of Pediatrics, Pediatric Neurology
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Ipoh
country: Malaysia
facility: Paediatric Department
state: Perak
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Cebu City
country: Philippines
facility: Cebu Doctors' University Hospital
state: Cebu
city: Sta. Cruz
country: Philippines
facility: Center for Neurodiagnostic and Therapeutic Services
state: Manila
city: Quezon City
country: Philippines
facility: Capitol Medical Center Inc.
state: National Capital Region
city: Cebu City
country: Philippines
facility: Cebu Doctors' University Hospital
city: Manila
country: Philippines
facility: University of Santo Tomas Hospital
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
city: Quezon City
country: Philippines
facility: Philippine Children's Medical Center
city: Gdansk
country: Poland
facility: Klinika Neurologii Rozwojowej
city: Kielce
country: Poland
facility: NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki
city: Krakow
country: Poland
facility: Wojewodzki Specjalistyczny Szpital Dzieciecy im. sw. Ludwika w Krakowie
city: Poznan
country: Poland
facility: Katedra i Klinika Neurologii Wieku Rozwojowego
city: Wroclaw
country: Poland
facility: Oddzial Neurologii Dzieciecej, Dolnoslaski Szpital Specjalistyczny im.T. Marciniaka
city: Bucuresti
country: Romania
facility: Spitalul clinic de copii Dr. Victor Gomoiu
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof. Dr. Al. Obregia"
city: Iasi
country: Romania
facility: Spitalul Clinic de Urgente pentru Copii "Sf. Maria",
city: Sibiu
country: Romania
facility: Spitalul de Psihiatrie Dr. Ghe. Preda
city: Timisoara
country: Romania
facility: Centrul Medical Dr. Bacos Cosma
city: Novi Sad
country: Serbia
facility: Institute for Child and Youth Healthcare of Vojvodina
state: Vojvodina
city: Belgrade
country: Serbia
facility: Mother and Child Healthcare Institute Dr Vukan Cupic
city: Belgrade
country: Serbia
facility: University Children's Hospital Belgrade
city: Kragujevac
country: Serbia
facility: Clinical Center of Kragujevac
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Izmir
country: Turkey
facility: Ege University Medical Faculty Department of Pediatrics Health and Diseases
state: Bornova
city: Trabzon
country: Turkey
facility: Karadeniz Technical University Faculty of Medicine Farabi Hospital
state: Farabi
city: Izmir
country: Turkey
facility: Izmir Tepecik Training and Research Hospital
state: Konak
city: Izmir
country: Turkey
facility: Behcet Uz Children Disease and surgery Training and research hospital
state: Konak
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
state: Pendik
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
state: Sihhiye/ankara
city: Dnipropetrovsk
country: Ukraine
facility: Komunalnyi zaklad "Dnipropetrovska dytiacha miska klinichna likarnia
city: Dnipropetrovsk
country: Ukraine
facility: Komunalnyi zaklad "Dnipropetrovska oblasna dytiacha klinichna likarnia"
city: Kharkiv
country: Ukraine
facility: Derzhavna ustanova "Instytut nevrolohii, psykhiatrii ta narkolohii
city: Kharkiv
country: Ukraine
facility: Derzhavna Ustanova Instytut Nevrolohii, Psykhiatrii ta Narkolohii NAMN Ukrainy,
city: Kyiv
country: Ukraine
facility: Derzhavnyi zaklad "Ukrainskyi medychnyi tsentr reabilitatsii ditei z
city: Odesa
country: Ukraine
facility: Komunalna ustanova "Odeskyi oblasnyi medychnyi tsentr psykhichnoho zdorovia",
city: Odesa
country: Ukraine
facility: Komunalna ustanova "Odeska oblasna dytiacha klinichna likarnia", Oblasnyi tsentr rannoi
city: S. Oleksandrivka
country: Ukraine
facility: Komunalna ustanova "Odeska oblasna psykhiatrychna likarnia 2",
city: Uzhgorod
country: Ukraine
facility: Oblasnyi klinichnyi tsentr neirokhirurhii ta nevrolohii, viddilennia neirokhirurhii 2,
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Antinew J, Pitrosky B, Knapp L, Almas M, Pitman V, Liu J, Craiu D, Modequillo M, Nordli D, Farkas V, Farkas MK. Pregabalin as Adjunctive Treatment for Focal Onset Seizures in Pediatric Patients: A Randomized Controlled Trial. J Child Neurol. 2019 Apr;34(5):248-255. doi: 10.1177/0883073818821035. Epub 2019 Jan 27.