A Safety, Efficacy, and Tolerability Trial of Pregabalin as Add-On Treatment in Pediatric Subjects <4 Years of Age With Partial Onset Seizures.

Partial Onset Seizures Clinical Trial

Official title:

A Double-blind, Placebo-controlled, Parallel-group, Multicenter Study Of The Efficacy And Safety Of Pregabalin As Adjunctive Therapy In Children 1 Month Through <4 Years Of Age With Partial Onset Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02072824
• Other study ID #: A0081042
• Secondary ID: 2013-003420-37
• Status: Completed
• Phase: Phase 3
• Start date: September 16, 2014
• Est. completion date: March 13, 2018

Study information

• Verified date: September 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the effectiveness of 2 doses of pregabalin to reduce seizure frequency as an add on therapy in pediatric subjects 1 month to <4 years of age with refractory partial onset seizures. It is hypothesized that both doses of pregabalin will demonstrate superior efficacy when compared to placebo by reducing the partial onset seizure frequency and that pregabalin will be safe and well tolerated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: March 13, 2018
• Est. primary completion date: March 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 3 Years

Eligibility

Inclusion Criteria:

• Subject must have 3 partial onset seizures in the month prior to screening.

• Subject must have 2 partial onset seizures during the 48 hour baseline phase.

• Signed Informed Consent.

• On 1-3 stable anti-epileptic drugs at screening.

Exclusion Criteria:

• Primary generalized seizures including clonic, tonic, clonic-tonic, absence, febrile seizures, and infantile spasms.

• Lennox-Gasteau, BECTS, and Dravet's syndrome.

• Status epliepticus within 1 year of screening.

• Any change in AED regimen with 7 days of screening.

• Progressive structural central nervous system (CNS) lesion or a progressive encephalopathy.

• Progressive errors of metabolism.

Related Conditions & MeSH terms

• Partial Onset Seizures
• Seizures

Intervention

Drug:
• Pregabalin Dose Level 1
Pregabalin liquid dosed daily three times a day in equally divided doses escalated to 7.0 mg/kg/day beginning at Randomization through Taper Phase then tapered to 3.5 mg/kg/day during 1 week Taper Phase
• Pregabalin Dose Level 2
Pregabalin liquid dosed daily three times a day in equally divided doses escalated to 14.0 mg/kg/day beginning at Randomization through Taper Phase then tapered to 3.5 mg/kg/day during 1 week Taper Phase
• Placebo
Placebo Liquid dosed three times daily beginning at Randomization through Taper Phase

Locations

Country	Name	City	State
Belarus	GU Republican Scientific and Practical Center Mother and Child	Minsk
Belgium	UZ Brussel	Brussels	Bruxelles Capitale
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska	Banja Luka
Bulgaria	UMHAT Dr. Georgi Stranski Ltd.	Pleven
Bulgaria	UMHAT "Sveti Georgi" Ltd.	Plovdiv
China	Beijing Children's Hospital	Beijing
China	The First Bethune Hospital of Jilin University	Changchun	Jilin
China	Children's Hospital of Fudan University	Shanghai	Shanghai
France	Hopital Raymond Poincare	Garches
Germany	Universitaetsklinikum Jena	Jena	Thueringen
Greece	University General Hospital Attikon	Athens
Greece	General Hospital of Thessaloniki Ippokratio	Thessaloniki
Hungary	Dr. Kenessey Albert Korhaz es Rendelointezet	Balassagyarmat
Hungary	Magyarorszagi Reformatus Egyhaz Bethesda Gyermekkorhaz, Gyermekneurologia	Budapest
Hungary	Semmelweis Egyetem, I. Sz. Gyermekgyogyaszati Klinika	Budapest
Hungary	Szent János Kórház es Észak Budai Egyesitett Kórházak	Budapest
Hungary	Szent Margit Kórház	Budapest
Hungary	Debreceni Egyetem Klinikai Központ	Debrecen
Israel	Pharmacy of The E. Wolfson Medical Center	Holon
Israel	The E. Wolfson Medical Center	Holon
Israel	Pharmacy of Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Lebanon	American University of Beirut Medical Center	Beirut
Lebanon	Saint George Hospital - University Medical Center	Beirut
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan
Philippines	Cebu Doctors' University Hospital	Cebu City	Cebu
Philippines	Perpetual Succour Hospital	Cebu City	Cebu
Philippines	Manila Doctors Hospital	Manila
Philippines	Metropolitan Medical Center	Manila
Philippines	University of Santo Tomas Hospital	Manila
Philippines	Philippine Children's Medical Center	Quezon City
Philippines	St. Luke's Medical Center	Quezon City
Romania	Centrul Medical Unirea	Bucuresti
Romania	Spitalul Clinic de Urgente pentru Copii "Sf. Maria"	Iasi
Russian Federation	FSFEI HE N.I. Pirogov RNRMU of Minzdrav of Russia	Moscow
Russian Federation	FSFEI HE N.I. Pirogov RNRMU of Minzdrav of Russia	Moscow
Russian Federation	Nizhmedklinika	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	Perm State Medical University n. a. acad. E.A. Vagner	Perm	Permskiy KRAY
Russian Federation	Perm State Medical University n. a. acad. E.A. Vagner	Perm
Russian Federation	"Baltiyskaya Medicyna" LLC	Saint Petersburg
Russian Federation	St. Petersburg State Pediatric Medical University	Saint Petersburg
Russian Federation	LLC Medical Technologies	Saint-Petersburg
Russian Federation	LLC Medical Technologies	Saint-Petersburg
Russian Federation	RSBHI Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	SHI Central Clinical Medical Unit	Ulyanovsk
Russian Federation	SHI Central Clinical Medical Unit	Ulyanovsk
Russian Federation	SHI Ulyanovsk Regional Children's Clinical Hospital n. a. Y.F.Goryachev	Ulyanovsk
Russian Federation	MAI Children's City Clinical Hospital 9	Yekaterinburg
Serbia	Mother and Child Healthcare Institute Dr Vukan Cupic	Belgrade
Serbia	University Children's Hospital Belgrade	Belgrade
Serbia	Institute for Child and Youth Healthcare of Vojvodina	Novi Sad	Vojvodina
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	Chang Gung Memorial Hospital- Kaohsiung branch	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Siriraj Hospital, Faculty of Medicine, Mahidol University	Bangkoknoi	Bangkok
Thailand	Phramongkutklao Hospital	Ratchathevee	Bangkok
Turkey	Eskisehir Osmangazi Universitesi Tip Fakultesi	Eskisehir
Turkey	Izmir Tepecik Training and Research Hospital	Izmir	Konak
Turkey	Karadeniz Teknik Universitesi Tip Fakultesi Farabi Hastanesi	Trabzon
Ukraine	Komunalnyi zaklad "Dnipropetrovska dytiacha miska klinichna likarnia #5"	Dnipro
Ukraine	Komunalnyi zaklad "Dnipropetrovska oblasna dytiacha klinichna likarnia"	Dnipro
Ukraine	Ivano-Frankivska oblasna dytiacha klinichna likarnia	Ivano-Frankivsk
Ukraine	DZ "Ukrainskyi medychnyi tsentr reabilitatsii ditei z orhanichnym urazhenniam	Kyiv
Ukraine	Oblasnyi klinichnyi tsentr neirokhirurhii ta nevrolohii,viddilennia neirokhirurhii #2	Uzhgorod
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Pediatric Epilepsy Center of Central Florida	Orlando	Florida
United States	Pediatric Neurology, PA	Orlando	Florida
United States	Road Runner Research, Ltd.	San Antonio	Texas
United States	Pediatric Epilepsy & Neurology Specialists, PA	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Countries where clinical trial is conducted

United States,  Belarus,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  China,  France,  Germany,  Greece,  Hungary,  Israel,  Korea, Republic of,  Lebanon,  Malaysia,  Philippines,  Romania,  Russian Federation,  Serbia,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events which occurred between first dose of study drug and up to end of study (up to Day 25) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.	Day 1 up to End of study (EOS) (maximum Day 25)
Other	Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events which occurred between first dose of study drug and up to end of study (up to Day 25) that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to drug was assessed by the investigator. AEs included both serious and non-serious adverse events.	Day 1 up to EOS (maximum Day 25)
Other	Number of Adverse Events by Severity	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs were classified according to the severity in 3 categories a) mild: AEs does not interfere with participant's usual function b) moderate: AEs interferes to some extent with participant's usual function c) severe: AEs interferes significantly with participant's usual function.	Day 1 up to EOS (maximum Day 25)
Other	Number of Participants With Laboratory Test Abnormalities	Abnormality Criteria: hemoglobin,hematocrit,red blood cells(RBC)count:<0.8*lower limit of normal[LLN],platelets:<0.5*LLN/>1.75*upper limit of normal[ULN]; leukocytes:<0.6*LLN/>1.5*ULN; lymphocytes,neutrophils, total protein,albumin, tetraiodothyronine,thyroid stimulating hormone:<0.8*LLN/>1.2*ULN; basophils,eosinophils,monocytes:>1.2*ULN; prothrombin [PT],PT international ratio:>1.1*ULN; aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,gamma glutamyl transferase:>0.3*ULN; bilirubin:>1.5*ULN; blood urea nitrogen,creatinine, cholesterol,triglycerides:>1.3*ULN; sodium: <0.95*LLN/>1.05*ULN; potassium,chloride,calcium,bicarbonate:<0.9*LLN/>1.1*ULN; glucose fasting:<0.6*LLN/>1.5*ULN; creatine kinase:>2*ULN;urine glucose,ketone,protein:>=1;urine WBC,RBC:>= 20/High Power Field[HPF]; urine casts,hyaline casts:>1/Low Power Field; urine bacteria:>20/HPF.	From Baseline up to EOS (maximum Day 25)
Other	Number of Participants With Vital Signs Abnormalities	Criteria for abnormalities in vital signs included: sitting/supine systolic blood pressure (SBP) values: maximum increase and decrease of greater than or equal to (>=) 30 millimeter of mercury (mmHg) from baseline; sitting/supine diastolic blood pressure (DBP) value: maximum increase and decrease of >=20 mmHg from baseline.	From Baseline (BL) up to EOS (maximum Day 25)
Other	Percentage of Participants With Abnormal Physical Examination Findings at Screening and End of Study	Physical examinations evaluated the following body systems/organs: abdomen; ears; extremities; eyes; general appearance; head; heart; lungs; lymph nodes; mouth; musculoskeletal; nose; skin and throat. Abnormalities in physical examination were based on investigator's discretion.	Screening and EOS (maximum Day 25)
Other	Percentage of Participants With Abnormal Neurological Examination Findings at Baseline and End of Study	Neurological examinations included: coordination; cranial nerve function (CNF); gait and station; level of consciousness (LOC); lower and upper extremity sensation; muscle strength; muscle tone; nystagmus; reflexes and speech. Abnormalities in neurological examination were based on investigator's discretion and also, some components of the neurological examination were not done for certain participants due to participant age or significant developmental impairment. Only those categories of neurological examination in which at least 10% of participants had an abnormality in any treatment group at any time point were reported in this outcome measure.	Baseline (BL) and EOS (maximum Day 25)
Other	Number of Participants With Electrocardiogram (ECG) Abnormalities	Criteria for abnormalities in ECG findings: 1) Time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS complex): >=140 milliseconds (msec); 2) The interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval): >=200 msec; 3) Time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTCF interval): absolute value 450 to <480 msec, 480 to <500 msec, >=500 msec; 4) Maximum QT interval: >=500 msec; 5) Maximum QTCB interval (Bazett's correction): 450 to< 480 msec, 480 to <500 msec, >=500 msec. Only those categories of ECG abnormalities in which participants were found abnormal (maximum QTCB interval 450-<480 msec), were reported in this outcome measure.	From screening up to EOS (maximum Day 25)
Primary	Log Transformed 24-Hour Seizure Rate for All Partial Onset Seizures During the Double-Blind Treatment Phase	All partial onset seizures experienced during treatment phase were recorded by central reader during the 48 to 72 hour video-electroencephalogram (EEG). Double Blind 24 hour EEG seizure rate for all partial onset seizures = ([Number of seizures in double blind 48 to 72 hour EEG assessment] divided by [number of hours of video-EEG monitoring])*24. The EEG assessment was done at the end of the fixed dose treatment. For log-transformation, the quantity 1 was added to the double blind 24 hour EEG seizure rate for all participants to account for any possible "0" seizure incidence. This resulted in final calculation as: log transformed (double-blind 24-hour EEG seizure rate + 1).	Day 1 up to Day 14
Secondary	Responder Rate: Percentage of Participants With at Least 50 Percent (%) or Greater Reduction From Baseline in 24-Hour Seizure Rate for All Partial Onset Seizures During the Double-Blind Treatment Phase	Responder Rate was defined as percentage of participants who had a 50% or greater reduction from baseline in 24-hour seizure rate during the double-blind treatment phase. Double Blind 24 hour EEG seizure rate for all partial onset seizures = ([Number of seizures in double blind 48 to 72 hour EEG assessment] divided by [number of hours of video-EEG monitoring])*24. The EEG assessment was done at the end of the fixed dose treatment.	Day 1 up to Day 14

External Links

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