A Safety, Efficacy and Tolerability Trial of Pregabalin as Add-On Treatment in Pediatric and Adult Subjects With Primary Generalized Tonic-Clonic (i.e., Grand Mal) Seizures.

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER TRIAL OF PREGABALIN AS ADJUNCTIVE THERAPY IN PEDIATRIC AND ADULT SUBJECTS WITH PRIMARY GENERALIZED TONIC-CLONIC SEIZURES - PROTOCOL A0081105

The study is designed to evaluate the safety, tolerability and efficacy of two doses of pregabalin as add-on treatment in pediatric and adult subjects with Primary Generalized Tonic-Clonic (PGTC) seizures as compared to placebo. It is hypothesized that both doses of pregabalin will demonstrated superior efficacy when compared to placebo by reducing PGTC seizure frequency and that pregabalin will be safe and well tolerated.

Study Overview

• Status: Completed
• Conditions: Generalized Tonic Clonic Seizures
• Intervention / Treatment: Drug: Pregabalin Dose Level 1; Drug: Pregabalin Dose Level 2; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck
  • Linz, Austria, 4021
    • AKH Linz
• Belarus
  • Vitebsk, Belarus, 210015
    • UZ Vitebsk Regional Childrens Clinical Centre
  • Vitebsk, Belarus, 210022
    • UZ Vitebsk Regional Childrens Clinical Centre
• Bosnia and Herzegovina
  • Canton Sarajevo
    • Sarajevo, Canton Sarajevo, Bosnia and Herzegovina, 71000
      • University Clinical Center Sarajevo
  • Canton Tuzla
    • Tuzla, Canton Tuzla, Bosnia and Herzegovina, 75000
      • University Clinical Center Tuzla
  • Herzegovinaneretva Canton
    • Mostar, Herzegovinaneretva Canton, Bosnia and Herzegovina, 88000
      • University Clinical Hospital Mostar
  • Republika Srpska
    • Prijedor, Republika Srpska, Bosnia and Herzegovina, 79101
      • Public Health Institution Hospital Dr Mladen Stojanovic
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Multiprofile Hospital for Active Treatment Puls AD
  • Pleven, Bulgaria, 5800
    • DCC Sv. Pantaleimon OOD
  • Pleven, Bulgaria, 5800
    • Military Medical Academy - Multiprofile Hospital for Active Treatment
  • Plovdiv, Bulgaria, 4000
    • MHAT Central Onco Hospital OOD
  • Ruse, Bulgaria, 7000
    • Medical Center Teodora
  • Sofia, Bulgaria, 1113
    • MHATNP Sveti Naum EAD
  • Sofia, Bulgaria, 1431
    • UMHAT Aleksandrovska
  • Sofia, Bulgaria, 1784
    • DCC Sveta Anna - Sofia
• China
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • The First Affiliated Hospital of Chongqing Medical University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Bethune Hospital of Jilin University
  • Shanghai
    • Shanghai, Shanghai, China, 201100
      • Shanghai Huashan Hospital, Neurology Department
• Croatia
  • Split, Croatia, 21000
    • University Hospital Center Split, Clinic for Neurology
• Denmark
  • Aarhus C, Denmark, 8000
    • Aarhus University Hospital
  • Odense C, Denmark, 5000
    • Odense University Hospital
• France
  • Amiens Cedex 1, France, 80054
    • CHU d'Amiens - Picardie
  • Rennes, France, 35033
    • CHRU de Rennes - Hôpital Pontchaillou
  • Rennes, France, 35033
    • CHU d'Amiens Hopital Pontchaillou
• Greece
  • Athens, Greece, 15125
    • Athens Medical Center
  • Athens, Greece, 15236
    • General Children's Hospital Penteli
  • Athens, Greece, 11528
    • Eginition Hospital
  • Thessaloniki, Greece, 54636
    • University General Hospital of Thessaloniki "Ahepa"
• Hungary
  • Budapest, Hungary, H-1083
    • Semmelweis Egyetem, I. Sz. Gyermekgyogyaszati Klinika
  • Hodmezovasarhely, Hungary, H-6800
    • Csongrad Megyei Egeszsegugyi Ellato Kozpont Hodmezovasarhely-Mako
  • Kistarcsa, Hungary, 2143
    • Pest Megyei Flór Ferenc Kórház
• India
  • Delhi
    • New Delhi, Delhi, India, 110076
      • Indraprastha Apollo Hospitals
  • Karnataka
    • Bangalore, Karnataka, India, 560034
      • St. John's Medical College Hospital
    • Mangalore, Karnataka, India, 575003
      • Mangala Hospital & Mangala Kidney Foundation
  • Maharashtra
    • Mumbai, Maharashtra, India, 400016
      • P D Hinduja National Hospital and Medical Research Centre
    • Nagpur, Maharashtra, India, 440012
      • Getwell Hospital and Research Institute
    • Pune, Maharashtra, India, 411011
      • KEM Hospital Research Centre
    • Pune, Maharashtra, India, 411004
      • Sahyadri Speciality Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Korea
    • Daegu, Korea, Korea, Republic of, 41931
      • Keimyung University Dongsan Hospital
• Lebanon
  • Beirut, Lebanon, NAP
    • Saint George Hospital - University Medical Center
  • El Chouf, Lebanon
    • Ain Wazein Medical Village
• Malaysia
  • Perak
    • Ipoh, Perak, Malaysia, 30990
      • Hospital Raja Permaisuri Bainun
• Montenegro
  • Bijelo Polje, Montenegro, 84000
    • Pzu Neuron
• Philippines
  • Cebu City, Philippines, 6000
    • Cebu Doctors' University Hospital, Rm Ph 7
  • Manila, Philippines, 1003
    • Metropolitan Medical Center
  • Manila, Philippines, 1008
    • University of Santo Tomas Hospital
  • Manila, Philippines, 1000
    • Manila Doctors Hospital
  • Quezon City, Philippines
    • St. Luke's Medical Center Cathedral Heights Building
  • Cebu
    • Cebu City, Cebu, Philippines, 6000
      • Cebu Doctors' University Hospital
    • Cebu City, Cebu, Philippines, 6000
      • Perpetual Succour Hospital
• Poland
  • Gdansk, Poland, 80-803
    • COPERNICUS Podmiot Leczniczy Spzoo
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska Synapsis
  • Katowice, Poland, 40-650
    • NZOZ Novo Med
  • Katowice, Poland, 40-749
    • Neuro-Care Gabriela Klodowska
  • Krakow, Poland, 31-223
    • NZOZ "HIPOKRATES II" Sp. z o.o.
  • Lublin, Poland, 20-090
    • Instytut Medycyny Wsi im. Witolda Chodzki w Lublinie
  • Poznan, Poland, 60-529
    • Solumed Centrum Medyczne
  • Swidnik, Poland, 21-040
    • NZOZ IGNIS dr n. med. Alicja Lobinska
  • Warsaw, Poland, 00-453
    • Lecznica Medyczna ''Zycie"
• Romania
  • Brasov, Romania, 500283
    • Centrul Medical de Diagnostic si Tratament Ambulator NEOMED
  • Bucuresti, Romania, 010042
    • CMI Neurologie, Neurofiziologie (EEG, EMG, PEC) Roceanu Adina Maria
  • Bucuresti, Romania, 030583
    • Sapiens Medical Center
  • Iasi, Romania, 700309
    • Spitalul Clinic de Urgente pentru Copii "Sf. Maria"
  • Iasi, Romania, 700309
    • Spitalul Clinic de Urgenta "Prof. Dr. Nicolae Oblu"
  • Sibiu, Romania, 550082
    • Spitalul de Psihiatrie "Dr. Gh. Preda"
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • TSBHI City Hospital No. 5 of Barnaul
  • Chelyabinsk, Russian Federation, 454048
    • MAHI of the Order of the Red Banner of Labor City Clinical Hospital No. 1
  • Moscow, Russian Federation, 129128
    • Non-State Healthcare Institution
  • Novosibirsk, Russian Federation, 630091
    • LLC City Neurological Center "Sibneiromed"
  • Perm, Russian Federation, 614990
    • Perm State Medical University n. a. acad. E.A. Vagner
  • Saint Petersburg, Russian Federation, 195112
    • SBHI of Saint Petersburg Psychoneurological Dispensary #5
  • Saint Petersburg, Russian Federation, 195176
    • SBHI of Saint Petersburg Psychoneurological Dispensary #5
  • Saint Petersburg, Russian Federation, 192019
    • FSBI V.M. Bekhterev National Research Medical Center for
  • Saint-Petersburg, Russian Federation, 191040
    • SPHI Leningrad Regional Psychoneurological Dispensary
  • Smolensk, Russian Federation, 214018
    • Regional State Budgetary Institution of Ministry of Health
  • Smolensk, Russian Federation, 214018
    • RSBHI Smolensk Regional Clinical Hospital
  • Smolensk, Russian Federation, 214019
    • GBOU VPO Smolensk State Medical University
  • Ulyanovsk, Russian Federation, 432026
    • SHI "Central Clinical Medical Unit
  • Ulyanovsk, Russian Federation, 432045
    • SHI "Central Clinical Medical Unit
  • Leningrad Region
    • Pgt. Roshchino, Leningrad Region, Russian Federation, 188820
      • SPHI Leningrad Regional Psychoneurological Dispensary
  • Nizhegorodskaya Oblast
    • Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation, 603159
      • Nizhmedklinika
  • Permskiy KRAY
    • Perm, Permskiy KRAY, Russian Federation, 614000
      • Perm State Medical University n. a. acad. E.A. Vagner
  • Republic OF Tatarstan
    • Kazan, Republic OF Tatarstan, Russian Federation, 420012
      • GBOU VPO "Kazan State Medical University" of Roszdrav
    • Kazan, Republic OF Tatarstan, Russian Federation, 420064
      • Republican Clinical Hospital
  • Stavropol Region
    • Pyatigorsk, Stavropol Region, Russian Federation, 357538
      • State Budgetary Healthcare Institution of Stavropol region
• Serbia
  • Belgrade, Serbia, 11000
    • University Children's Hospital
  • Belgrade, Serbia, 11000
    • Institute for Mental Health
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Vojvodina
    • Novi Sad, Vojvodina, Serbia, 21000
      • Institute for Child and Youth Healthcare of Vojvodina
• Slovakia
  • Hlohovec, Slovakia, 92001
    • Neurologicka ambulancia MUDr. Eva Gasparova
  • Hlohovec, Slovakia, 92001
    • Nemocnica s poliklinikou Hlohovec, s.r.o.
• Spain
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
• Turkey
  • Eskisehir, Turkey, 26480
    • Eskisehir Osmangazi University Medical Faculty Department Of Neurology
  • Izmir, Turkey, 35340
    • Dokuz Eylul Ün. Tip Fakültesi İç Hastalıkları
  • Manisa, Turkey, 45010
    • Celal Bayar University School of Medicine, Neurology Department
  • UST Kaynarca/pendik
    • Istanbul, UST Kaynarca/pendik, Turkey, 34899
      • Marmara University Pendik Training and Research Hospital
• Ukraine
  • Dnipro, Ukraine, 49027
    • Komunalnyi zaklad "Dnipropetrovska dytiacha miska klinichna likarnia No. 5"
  • Dnipro, Ukraine, 49100
    • Komunalnyi zaklad "Dnipropetrovska oblasna dytiacha klinichna likarnia"
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivska oblasna dytiacha klinichna likarnia
  • Kharkiv, Ukraine, 61068
    • Derzhavna ustanova "Instytut nevrolohii, psykhiatrii ta narkolohii
  • Kharkiv, Ukraine, 61068
    • Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasna klinichna psykhiatrychna li
  • Kyiv, Ukraine, 04209
    • Derzhavnyi zaklad "Ukrainskyi medychnyi tsentr reabilitatsii ditei z
  • Lviv, Ukraine, 79010
    • Komunalnyi zaklad Lvivskoi oblasnoi rady "Lvivska oblasna klinichna likarnia"
  • Odesa, Ukraine, 65006
    • Komunalne nekomertsiine pidpryiemstvo "Odeskyi oblasnyi
  • Uzhgorod, Ukraine, 88018
    • Oblasnyi klinichnyi tsentr neirokhirurhii ta nevrolohii,
  • Zaporizhzhia, Ukraine, 69068
    • Komunalna ustanova "Miska klinichna likarnia #2", nevrolohichne viddilennia
  • Komintern. R-N, Odeska OBL.
    • S. Oleksandrivka, Komintern. R-N, Odeska OBL., Ukraine, 67513
      • Komunalna ustanova "Odeska oblasna psykhiatrychna likarnia 2"
• United Kingdom
  • London, United Kingdom, E1 2AT
    • Barts Health NHS Foundation Trust, The Royal London Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
  • Swansea, United Kingdom, SA6 6NL
    • ABMU Local Health Board, Morriston Hospital
  • WEST Midlands
    • Birmingham, WEST Midlands, United Kingdom, B15 2FG
      • The Barberry National Centre for Mental Health
• United States
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Axcess Medical Research
    • Orlando, Florida, United States, 32819
      • Pediatric Neurology, PA
    • Orlando, Florida, United States, 32819
      • Pediatric Epilepsy Center of Central Florida
    • Port Charlotte, Florida, United States, 33952
      • Medsol Clinical Research Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Alexian Brothers Center for Psychiatric Research
    • Hoffman Estates, Illinois, United States, 60169
      • Chinmay K. Patel, D.O.
    • Hoffman Estates, Illinois, United States, 60169
      • St. Alexius Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Ohio Clinical Research Partners, LLC
  • Texas
    • San Antonio, Texas, United States, 78249
      • Road Runner Research, Ltd
    • Temple, Texas, United States, 76508
      • Scott & White Memorial Hospital And Clinic
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Seizures classified as Primary Generalized Tonic Clonic Seizures
• Must have at least 1 PGTC seizure in the 8 weeks prior to screening
• Must have a minimum of 3 PGTC seizures during the 8-week baseline phase and at least 1 PGTC in each 4-week period of the baseline phase
• Currently receiving adequate and stable dosage of 1 to 3 anti-epileptic treatments (stable within 28 days of screening)
• Signed informed consent and assent if a minor
• Ability to comply with daily seizure and dosing diary requirements and all study procedures

Exclusion Criteria:

• A current diagnosis of febrile seizures, or seizures related to an ongoing acute medical illness
• Focal seizures (simple partial, complex partial, or partial becoming secondarily generalized)
• Status Epilepticus within 1 year prior to screening
• Lennox-Gastaut syndrome, infantile spasms, Benign Epilepsy with Centrotemporal Spikes (BECTS) and Dravet syndrome
• Seizures related to drugs, alcohol, or acute medical illness
• Any change in anti-epileptic treatment regimen (type of medication or dose; VNS alteration) within 28 days of the screening visit or during the baseline phase
• Progressive or potentially progressive structural CNS lesion or a progressive encephalopathy.
• Progressive inborn errors of metabolism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo, either liquid or capsule, dosed twice daily beginning at Randomization to End of Study/Early Termination.
Experimental: Study Drug Level 1	Drug: Pregabalin Dose Level 1; Pregabalin, either liquid or capsule, dosed twice daily, escalated up to a maximum of 300 mg/day beginning at Randomization to Taper Phase, then tapered down to a maximum dose of 150 mg/day during 1 week Taper Phase to End of Study/Early Termination.; Other Names: Lyrica Dose Level 1
Experimental: Study Drug Level 2	Drug: Pregabalin Dose Level 2; Pregabalin, either liquid or capsule, dosed twice daily, escalated up to a maximum of 600 mg/day beginning at Randomization to Taper Phase, then tapered down to a maximum of 150 mg/day during 1 week Taper Phase to End of Study/Early Termination.; Other Names: Lyrica Dose Level 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Log-transformed (Log) 28-day Seizure Rate for All Primary Generalized Tonic-Clonic (PGTC) Seizures During 12-Week Double-Blind Treatment Phase	All PGTC seizures experienced during treatment phase were recorded by the participants or their parents/legal guardian in a daily seizure diary. 28-day seizure rate for all PGTC seizures= ([number of seizures in the double blind treatment phase] divided by [number of days in double blind treatment phase minus {-} number of missing diary days in treatment phase])*28. For log-transformation, the quantity 1 was added to the 28-day seizure rate for all participants to account for any possible "0" seizure incidence. This resulted in final calculation as: log transformed (28-day seizure rate +1).	Day 1 up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 50 Percent (%) or Greater Reduction From Baseline in 28-day Primary Generalized Tonic-clonic (PGTC) Seizure Rate During the 12-Week Double-blind Treatment Phase	Percentage of participants with 50% or greater reduction from baseline in 28-day seizure rate during the 12 week double blind treatment phase were reported. 28-day seizure rate for all PGTC seizures= ([number of seizures in the double blind treatment phase] divided by [number of days in double blind treatment phase minus {-} number of missing diary days in treatment phase])*28.	Day 1 up to Week 12

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Driscoll J, Almas M, Gregorian G, Kyrychenko A, Makedonska I, Liu J, Patrick J, Scavone JM, Antinew J; 1105 Study Group. Pregabalin as adjunctive therapy in adult and pediatric patients with generalized tonic-clonic seizures: A randomized, placebo-controlled trial. Epilepsia Open. 2021 Jun;6(2):381-393. doi: 10.1002/epi4.12492. Epub 2021 May 16.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2013
• Primary Completion (Actual): February 20, 2019
• Study Completion (Actual): February 20, 2019

Study Registration Dates

• First Submitted: November 27, 2012
• First Submitted That Met QC Criteria: December 10, 2012
• First Posted (Estimate): December 12, 2012

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Epilepsy; Safety; Efficacy; Tolerability; Pregabalin; Placebo Controlled; Blinded; Lyrica; Adjunctive treatment; Primary Generalized Tonic Clonic Seizures
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: A0081105; 2010-023263-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No