A 12-Month Study To Evaluate The Safety And Tolerability Of Pregabalin As Add-On Therapy In Pediatric Subjects 1 Month To 16 Years Of Age With Partial Onset Seizures And Pediatric And Adult Subjects 5 To 65 Years Of Age With Primary Generalized Tonic-Clonic Seizures
- Conditions
- Epilepsy, Partial SeizuresEpilepsy, Primary Generalized Tonic-Clonic Seizures
- Interventions
- Registration Number
- NCT01463306
- Lead Sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Brief Summary
Study A0081106 is a 12-month open-label study to evaluate the long term safety and tolerability of pregabalin as add-on therapy in pediatric subjects 1 month to 16 years of age with partial onset seizures and pediatric and adult subjects 5 to 65 years of age with primary generalized tonic-clonic seizures. Pregabalin will be administered in equally divided daily doses for 1 year, in either capsule or liquid oral formulation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 605
- Subjects and/or parent(s)/legally acceptable representative must be considered willing and able to sign consent, and complete daily dosing and seizure diaries and complete all scheduled visits.
- Male and female epilepsy subjects, 1 month to 65 years of age inclusive on the date of the Screening Visit.
- Diagnosis of epilepsy with seizures classified as simple partial, complex partial, or partial becoming secondarily generalized, or primary generalized tonic-clonic seizures according to the International League Against Epilepsy (ILAE 2010) Diagnosis Criteria.
- Partial onset seizure subjects must have had an average of at least 3 seizures per 28 day period in the 3 months prior to screening.
- Currently receiving a stable dose of 1 to 3 antiepileptic drugs (stable within 28 days prior to screening).
- Lennox-Gastaut syndrome, Infantile Spasms, Absence seizures, BECT (Benign Epilepsy with Centrotemporal Spikes), and Dravet syndrome,
- A current diagnosis of febrile seizures or any febrile seizure within 1 year of screening.
- Status epilepticus within 1 year prior to visit 1.
- Seizures related to drugs, alcohol, or acute medical illness.
- Progressive structural CNS lesion or a progressive encephalopathy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Open Pregabalin Pregabalin open label flexible dose
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment Emergent Adverse Events (AEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Related AEs and Treatment Related SAEs Baseline (Day 1) up to 13 Months 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 are events between first dose of study drug and up to 28 days after last dose of study drug (up to 13 months) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.
Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings up to 12 Months Baseline up to 12 Months Physical examination assessed: general appearance, dermatological, head and eyes, ears, nose, mouth, and throat, pulmonary, cardiovascular, abdominal, genitourinary (optional), lymphatic, musculoskeletal/extremities. Neurological examination assessed: level of consciousness, mental status, cranial nerve assessment, muscle strength and tone, reflexes, pin prick and vibratory sensation, coordination and gait. Investigator judged clinically significant change from baseline in physical and neurological examination findings.
Number of Participants Meeting Pre-defined Criteria for Vital Signs Abnormalities Baseline up to 12 months Pre-defined criteria of vital signs abnormalities: maximum (max.) increase or decrease from baseline in sitting/supine systolic blood pressure (SBP) \>=30 millimeter of mercury (mmHg); maximum increase or decrease from baseline in sitting/supine diastolic blood pressure (DBP) \>=20 mmHg.
Number of Participants With Tanner Staging Evaluation at Baseline Baseline (Day 1) Tanner stage defines physical measurements of development based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males), with values ranging from stage 1 (pre-pubertal characteristics) to stage 5 (adult or mature characteristics).
Number of Participants With Tanner Staging Evaluation at Month 12 Month 12 Tanner stage defines physical measurements of development based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males), with values ranging from stage 1 (pre-pubertal characteristics) to stage 5 (adult or mature characteristics).
Number of Participants With >=7 Percent (%) Change From Baseline in Body Weight up to 12 Months Baseline up to 12 Months In this outcome measure number of participants with increase and decrease of \>=7% in body weight, from baseline up to 12 months are reported.
Absolute Values for Body Height at Baseline Baseline Absolute Values for Body Height at Month 12 Month 12 Number of Participants With Incidence of Laboratory Abnormalities Baseline up to 12 Months Criteria for laboratory abnormalities: Hemoglobin (Hgb), hematocrit, red blood cell(RBC) count: \<0.8\*lower limit of normal(LLN), platelet: \<0.5\*LLN/greater than (\>)1.75\*upper limit of normal (ULN), white blood cell (WBC): \<0.6\*LLN/\>1.5\*ULN, lymphocyte, neutrophil- absolute/%:\<0.8\*LLN/\>1.2\*ULN, basophil, eosinophil, monocyte- absolute/%:\>1.2\*ULN; total/direct/indirect bilirubin \>1.5\*ULN, aspartate aminotransferase (AT), alanine AT, gammaglutamyl transferase, alkaline phosphatase:\> 3.0\*ULN, total protein, albumin: \<0.8\*LLN/\>1.2\*ULN; thyroxine, thyroid stimulating hormone \<0.8\*LLN/\>1.2\*ULN; cholesterol, triglycerides:\> \>1.3\*ULN; blood urea nitrogen, creatinine:\>1.3\*ULN; sodium \<0.95\*LLN/\>1.05\*ULN, potassium, chloride, calcium: \<0.9\*LLN or \>1.1\*ULN; glucose \<0.6\*LLN/\>1.5\*ULN, creatine kinase\>2.0\*ULN; urine (specific gravity \<1.003/\>1.030, pH \<4.5/\>8, glucose, ketones, protein: \>=1, WBC, RBC:\>=20, bacteria \>20, hyaline casts/casts \>1); prothrombin (PT), PT international ratio\>1.1\*ULN.
Number of Participants With Maximum Change From Baseline up to 12 Months in 12-Lead Electrocardiogram (ECG) Parameters Baseline up to 12 Months Categories for which data is reported are: 1) maximum (max) PR interval increase from baseline (IFB) (millisecond \[msec\]) percent change (PctChg) \>=25/50%; 2) maximum QRS complex increase from baseline (msec) PctChg\>=50%; 3) maximum QTcB interval (Bazett's correction) increase from baseline (msec): change \>=30 to \<60; change \>=60; 4) maximum QTcF interval (Fridericia's correction) increase from baseline (msec): change \>=30 to \<60; change \>=60. 'PctChg\>=25/50%': \>= 25% increase from baseline when baseline ECG parameter is \> 200 msec, and is \>= 50% increase from baseline when baseline ECG parameter is non-missing and \<=200 msec.
28-Days Seizure Rate at Week 1 Week 1 28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.
28-Days Seizure Rate at Month 1 Month 1 28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.
28-Days Seizure Rate at Month 2 Month 2 28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.
28-Days Seizure Rate at Month 4 Month 4 28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.
28-Days Seizure Rate at Month 6 Month 6 28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.
28-Days Seizure Rate at Month 9 Month 9 28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.
28-Days Seizure Rate at Month 12/Early Termination Month 12/Early Termination 28-days seizure rate was defined as number of seizures per 28-day period. 28-days seizure rate have been reported separately for partial onset seizure and primary generalized tonic clonic seizure. Partial onset seizure: a seizure that starts in one area of the brain. This kind of seizure is brief, lasting seconds to less than 2 minutes. Primary generalized tonic clonic seizure: a seizure that starts in one area of the brain, then spreads to both sides of the brain as a tonic-clonic seizure and usually last 1 to 3 minutes.
- Secondary Outcome Measures
Name Time Method Number of Participants With Suicidal Ideation as Per Columbia Suicide Severity Rating Scale (C-SSRS) Mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) Baseline (Day 1), Post-baseline on Day 1 up to 12 Months Number of participants with C-CASA code 4 are reported. C-SSRS responses mapping to C-CASA suicidal ideation code 4 are as follows: "Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with any methods (not plan) without intent to act", "active suicidal ideation with some intent to act, without specific plan", "active suicidal ideation with some intent to act, without specific plan".
Number of Participants With Suicidal Behavior as Per Columbia Suicide Severity Rating Scale (C-SSRS) Mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) Baseline (Day 1), Post-baseline up to 12 Months Number of participants with C-CASA code 1 or 2 or 3 are reported. C-SSRS responses mapping to C-CASA suicidal behavior codes 1, 2, or 3 are as follows: (1) completed suicide; (2) suicide attempt (response of "Yes" on "actual attempt"); (3) preparatory acts toward imminent suicidal behavior ("Yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior").
Number of Participants as Per Reliable Change Index (RCI) Category for Cogstate Detection Task Month 12 CogState brief battery consisted of 2 tasks- detection and pediatric identification task using a laptop computer with external response buttons. Prior tasks, participants were briefed rules, given an interactive demonstration and a sufficient number of practice trials. For each task, participant responded "yes" using a response button with dominant hand. Participants had to "respond as fast and as accurately as possible." Detection task: measured simple reaction time to assess psychomotor function. Participant pressed a "YES" response key as soon as they detected an event (ie, a card turning face up presented in the center of the computer screen). A participant's RCI was calculated by dividing the change from individual baseline score by (\[square root 2\] times WSD), where WSD is within-subject standard deviation from Cogstate detection task normative data. Improvement in cognition when RCI \<=-1.65, decline in cognition when RCI =\>1.65.
Number of Participants as Per Reliable Change Index Category for Cogstate Pediatric Identification Task Month 12 CogState brief battery consisted of 2 tasks-detection and pediatric identification task using a laptop computer with external response buttons. Prior tasks, participants were briefed rules, given an interactive demonstration and a sufficient number of practice trials. For each task, participant responded "yes" using a response button with dominant hand. Participants had to "respond as fast and as accurately as possible." Pediatric identification task: measured choice reaction time to assess visual attention. An event (a card turning face up) occurred in center of computer screen and participant decided if event met a predefined and unchanging criterion (is the color of the card black?); answered "YES" if criterion was met. A participant's RCI was calculated by dividing the change from individual baseline score by (\[square root 2\] times WSD),WSD=within-subject standard deviation from Cogstate task normative data. Improvement in cognition: RCI \<=-1.65, decline in cognition: RCI =\>1.65.
Trial Locations
- Locations (145)
Center for Neurosciences
🇺🇸Tucson, Arizona, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Axcess Medical Research
🇺🇸Loxahatchee Groves, Florida, United States
Laszlo J. Mate, M.D., P.A.
🇺🇸North Palm Beach, Florida, United States
Pediatric Epilepsy Center Of Central Florida
🇺🇸Orlando, Florida, United States
Pediatric Neurology, PA
🇺🇸Orlando, Florida, United States
Tallahassee Neurological Clinic
🇺🇸Tallahassee, Florida, United States
Pediatric Epilepsy and Neurology Specialists, PA
🇺🇸Tampa, Florida, United States
Hawaii Pacific Neuroscience
🇺🇸Honolulu, Hawaii, United States
Scroll for more (135 remaining)Center for Neurosciences🇺🇸Tucson, Arizona, United States