Safety and Efficacy of Lacosamide as Additional Therapy in Patients Suffering From Epileptic Tonic-Clonic Seizures (VALUE)

• ClinicalTrials.gov Identifier: NCT02408549
• Recruitment Status: Completed
• First Posted: April 3, 2015
• Results First Posted: December 14, 2023
• Last Update Posted: December 14, 2023
• Sponsor: UCB BIOSCIENCES, Inc.
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES, Inc. )

Tracking Information

• First Submitted Date: March 31, 2015
• First Posted Date: April 3, 2015
• Results First Submitted Date: September 28, 2023
• Results First Posted Date: December 14, 2023
• Last Update Posted Date: December 14, 2023
• Actual Study Start Date: August 3, 2015
• Actual Primary Completion Date: March 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 17, 2023)

• Number of Study Participants With Treatment-emergent Adverse Events (TEAEs) Over the Duration of the Treatment Period [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years) ]
  AEs were considered treatment-emergent if event had onset on or after date of first study medication dose in EP0012 and within 30 days following last study medication dose or events whose intensity worsened on or after date of first study medication dose and within 30 days following date of last study medication administration. Adverse Events were reported spontaneously by the participant and/or caregiver or observed by the investigator.
• Number of Study Participants Withdrawn Due to TEAEs [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years) ]
  AEs were considered treatment-emergent if event had onset on or after date of first study medication dose in EP0012 and within 30 days following last study medication dose or events whose intensity worsened on or after date of first study medication dose and within 30 days following date of last study medication administration. Adverse Events were reported spontaneously by the participant and/or caregiver or observed by the investigator.
• Number of Study Participants With New Appearance of Absence and/or Myoclonic Seizures During the Treatment Period [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years) ]
  The number of study participants with appearance of new absence and/or myoclonic seizure types experienced during the Treatment Period but who did not experience in Combined Baseline Period or in seizure classification history, before taking LCM were reported. To determine appearance of new seizure type, the Combined Baseline Period was used. Thus, the participants who directly enrolled into EP0012, the Baseline absence, and/or myoclonic seizure data from SP0982's 4-week Prospective Baseline Period were combined with any reported Baseline absence, and myoclonic seizure information in the daily seizure diary from EP0012 (reported before first dose in EP0012) to recalculate the study participant's Baseline variables such as days with absence, and/or myoclonic seizures per 28 days.
• Number of Study Participants With an Increase of up to 25% in Days With Absence Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period ]
  The number of participants experiencing an increase of up to 25% in the number of days with absence seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with absence seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012.
• Number of Study Participants With an Increase of Greater Than (>)25% to 50% in Days With Absence Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period ]
  The number of participants experiencing an increase of >25% to 50% in the number of days with absence seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with absence seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012.
• Number of Study Participants With an Increase of >50% to 75% in Days With Absence Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period ]
  The number of participants experiencing an increase of >50% to 75% in the number of days with absence seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with absence seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012.
• Number of Study Participants With an Increase of >75% in Days With Absence Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period ]
  The number of participants experiencing an increase of >75% in the number of days with absence seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with absence seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012.
• Number of Study Participants With an Increase of up to 25% in Days With Myoclonic Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period ]
  The number of participants experiencing an increase of up to 25% in the number of days with myoclonic seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with myoclonic seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012.
• Number of Study Participants With an Increase of >25% to 50% in Days With Myoclonic Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period ]
  The number of participants experiencing an increase of >25% to 50% in the number of days with myoclonic seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with myoclonic seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012.
• Number of Study Participants With an Increase of >50% to 75% in Days With Myoclonic Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period ]
  The number of participants experiencing an increase of >50% to 75% in the number of days with myoclonic seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with myoclonic seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012.
• Number of Study Participants With an Increase of >75% in Days With Myoclonic Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years), compared to the Prospective SP0982 Baseline Period ]
  The number of participants experiencing an increase of >75% in the number of days with myoclonic seizures per 28 days during the Treatment Period compared to the Prospective Baseline Period (for those participants with myoclonic seizure data reported in the 4-week Prospective Baseline Period in SP0982) were reported. This period started on the day of Visit 1 of SP0982 and ended the day before Visit 2 of SP0982. For the direct enrollers into EP0012, Prospective Baseline ended the day before Visit 1 (or prior to first dose) of EP0012.
• Percentage of Study Participants With at Least 50% Worsening in Days With Absence Seizures [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years) ]
  Seizure worsening was defined as a participant experiencing >=50% increase in the number of days with absence seizures per 28 days from Prospective Baseline. Percentages for seizure worsening were based on those participants who have reported a history of or an occurrence of absence seizures in Prospective Baseline or the Treatment Period.
• Percentage of Study Participants With at Least 50% Worsening in Days With Myoclonic Seizures [ Time Frame: From Visit 1 (Week 0) to End of Treatment Period (up to approximately 5 years) ]
  Seizure worsening was defined as a participant experiencing >=50% increase in the number of days with myoclonic seizures per 28 days from Prospective Baseline. Percentages for seizure worsening were based on those participants who have reported a history of or an occurrence of myoclonic seizures in Prospective Baseline or the Treatment Period.

Original Primary Outcome Measures (submitted: March 31, 2015)

• Number of subjects experiencing at least one Adverse Event (AE) during the study (up to 5 years) [ Time Frame: During the study (up to 5 years) ]
  Adverse Events will be reported spontaneously by the subject/ caregiver or observed by the investigator.
• Number of subjects withdrawing due to Adverse Events (AEs) during the study (up to 5 years) [ Time Frame: During the study (up to 5 years) ]
  Adverse Events will be reported spontaneously by the subject/ caregiver or observed by the investigator.
• Number of subjects experiencing at least one Serious Adverse Event (SAE) [ Time Frame: During the study (up to 5 years) ]
  Serious Adverse Events will be reported spontaneously by the subject/ caregiver or observed by the investigator.

Current Secondary Outcome Measures (submitted: November 17, 2023)

• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Hemoglobin) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the Statistical Analysis Plan (SAP) as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Hematology parameter, Hemoglobin were those that were observed post-Baseline (BL) during the Treatment Period but not present at Baseline. For the age range, '2 years (y) to <17 years', the abnormality criteria were '<=95' grams/deciliter (g/dL) (Low) and '>160' g/dL (High). For age range, '>=17 years', the abnormality Criteria were '<=85% of lower limit of normal (LLN)' value (Low) and '>=115% of upper limit of normal (ULN)' value (High) of Hemoglobin in blood.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Hematocrit) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Hematocrit were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, '2 years to <17 years', the abnormality criteria were '<=29%' (Low) and '>47%' (High) hematocrit values. For age range, '>=17 years', the abnormality criteria were '<=85% of LLN' (Low) and '>=115% of ULN' (High) of Hematocrit values in blood.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Platelets) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Platelet count were those that were observed post-BL during the Treatment Period but not present at BL. For the age range of '>1 month', the abnormality criteria were '<=100' 10^9/L and '>=600' 10^9/L of Platelets count value.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Erythrocytes) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Erythrocytes parameter were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, '>=2years', the abnormality criteria were '<3.5' 10^12/L of Erythrocytes value in blood. Early Termination Visit (TV) was last visit in the study (up to approximately 5 years).
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Leukocytes) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Leukocytes were those that were observed post-BL during the Treatment Period but not present at BL. For all age ranges, the abnormality criteria were '<=3.0' 10^9/L (Low) and '>= 16.0' 10^9/L (High) of Leukocytes values in blood.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Basophils Absolute) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Basophils Absolute were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, '>1 month', the abnormality criteria were '>=0.4' 10^9/L of Basophils in blood.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Eosinophils Absolute) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Eosinophils Absolute were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, '>1 month', the abnormality criteria were '>=1.0' 10^9/L of Eosinophils in the blood.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Lymphocytes Absolute) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Lymphocytes Absolute were those that were observed post-Baseline (BL) during the Treatment Period but not present at Baseline. For the age range, '2 years - <6 years', the abnormality criteria were '<0.7' 10^9/L (Low) and '>6.9' 10^9/L (High). For age range, '>=6 years', the abnormality criteria were '<0.6' 10^9/L (Low) and '>5.0' 10^9/L (High) for Lymphocytes Absolute in the blood.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Monocytes Absolute ) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Monocytes Absolute were those that are observed post-BL during the Treatment Period but not present at BL. For the age range, '>1 month', the abnormality criteria was '>=2.0' 10^9/L of Monocytes in blood.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Neutrophils Absolute) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Neutrophils Absolute were those that were observed post-BL during the Treatment Period but not present at BL. For the age range, '>1 month', the abnormality criteria was '<1.5' 10^9/L of Neutrophils in blood.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Calcium) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Calcium were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '1 year -<17 years', the abnormality criteria were '<=1.85' millimoles per litre (mmol/L) and '>=2.95' mmol/L. For age range, '>=17 years', the abnormality criteria was '<=1.9 mmol/L' and '>=2.75 mmol/L' of serum Calcium.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Sodium) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Sodium were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '>1 month', the abnormality criteria were '<127' mmol/L (Low) and '>151' mmol/L (High) of serum Sodium.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Potassium) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Potassium were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '>=1 year', the abnormality criteria were '<= 3.0' mmol/L (Low) and '>= 6.0' mmol/L (High) of serum Potassium.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Chloride) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Chloride were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '>1 month', the abnormality criteria were '<=90' mmol/L (Low) and '>=112' mmol/L (High) of serum Chloride.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Bicarbonate) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Bicarbonate were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '>1 month-<17 years', the abnormality criteria were '<15' mmol/L (Low) and '>38' mmol/L (High). For age range, '>=17 years', the abnormality criteria were '<18' mmol/L (Low) and '>38' mmol/L (High) of serum Bicarbonate.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Creatinine) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Creatinine were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '1-<10 years', the abnormality criteria were '>106.8' micromole per litre (umol/L), for '10-<16 years', the abnormality criteria were '>159.12' umol/L and for '>=16 years', the abnormality criteria was '>=176.8' umol/L for serum Creatinine.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Aspartate Aminotransferase) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Aspartate Aminotransferase (AST) were those that were observed post- BL during the Treatment Period but not present at Baseline. For all ages, the abnormality criteria were specified as '≥3.0 units per litre (U/L) x ULN' (High A), '≥5.0 U/L x ULN' (High B), and '≥10.0 U/L x ULN' (High C) of serum AST.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Alanine Aminotransferase) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Alanine Aminotransferase (ALT) were those that were observed post- BL during the Treatment Period but not present at Baseline. For all ages, the abnormality criteria were specified as '≥3.0 U/L x ULN' (High A), '≥5.0 U/L x ULN' (High B), and '≥10.0 U/L x ULN' (High C) of serum ALT.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Chemistry Parameters (Total Bilirubin) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Total Bilirubin were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '>1 month', the abnormality criteria was '≥34.208' umol/L of serum Bilirubin.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Alkaline Phosphatase) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Alkaline Phosphatase were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '4 years -<10 years', the abnormality criteria was '>=834 U/L', for '10 years -<17 years', the abnormality criteria was '>=1761 U/L' and for '>=17 years', the abnormality criteria was '>=3.0 U/L x ULN' of serum alkaline phosphatase.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Gamma Glutamyl Transferase) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Gamma Glutamyl Transferase (GGT) were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '1 year-<13 years', the abnormality criteria was '>=66' U/L (High A), for '13 years-<17 years', the abnormality criteria was '>=126' U/L (High B) and for '>=17 years', the abnormality criteria was '>=3.0 U/L x ULN' (High C) of serum GGT.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Glucose) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Glucose were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '>1 month-<17 years', the abnormality criteria were from '<2.775' mmol/L (Low) and '>=9.99' mmol/L (High). For age range, '>=17 years', the abnormality criteria were '<2.775' mmol/L (Low) and '>=11.1' mmol/L (High) of serum Glucose.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Albumin) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Albumin were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '>=1 year to <17 years', the abnormality criteria were '<24' g/L and '>84' g/L and for age range, '>=17 years', the abnormality criteria was '<26' g/L of serum albumin.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Total Protein) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Total Protein were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '1 year to <17 years', the abnormality criteria were '<43' g/L and '>120' g/L. For age range, '>=17 years', the abnormality criteria were '<43' g/L and '>130' g/L of serum protein.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Phosphate) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA laboratory results of Phosphate were those that are observed post- BL during the Treatment Period but not present at Baseline. For the age range, '1 year-<17 years', the abnormality criteria were from '<0.5814' mmol/L (Low) and '>2.3902' mmol/L (High). For age range, '>=17 years', the abnormality Criteria were '<=0.646' mmol/L (Low) and '>=1.938' mmol/L (High) of serum phosphate.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead Electrocardiogram (ECG) Parameter (QT Interval) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA ECG results of QT interval parameter were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '1 month (m)-<12 years', the abnormality criteria were '>=500 milliseconds (ms)' (Abnormal (Abn) A). For age range, '>=12 years', the abnormality criteria were '>=500 ms' (Abn B) or '>=60 ms increase from Baseline' (Abn C). The abnormality in QT interval was observed at Week 0 as the participant was rolled over from SP0982 study and was constantly having abnormal ECG parameters while in SP0982 and EP0012.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QTc(F) Interval) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA ECG results of QTc(F) interval were those that are observed post- BL during the Treatment Period but not present at Baseline. For the age range '3 years -<12 years' and '>=12 years- <17 years', the abnormality criteria were from '>440 ms' (Abn A) and '>15% increase from Baseline' value (Abn B). For age range, '>=17 years', the abnormality Criteria were '>450 ms' (Abn C), '>480 ms' (Abn D), '>500 ms' (Abn E) or '>=60 ms increase from Baseline' value (Abn F). The abnormality in QTc(F) interval was observed at Week 0 as the participant was rolled over from SP0982 study and was constantly having abnormal ECG parameters while in SP0982 and EP0012.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QTc(B) Interval) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA ECG results of QTc(B) interval were those that are observed post- BL during the Treatment Period but not present at Baseline. For the age range '3 years -<12 years' and '>=12 years- <17 years', the abnormality criteria were '>450 ms' (Abn A) and '>15% increase from Baseline' value (Abn B). For age range, '>=17 years', the abnormality criteria were '>450 ms' (Abn C), '>480 ms' (Abn D), '>500 ms' (Abn E) or '>=60 ms increase from Baseline' value (Abn F). The abnormality in QTc(B) interval was observed at Week 0 as the participant was rolled over from SP0982 study and was constantly having abnormal ECG parameters while in SP0982 and EP0012.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (PR Interval) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA ECG results of PR interval were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '3 years -<12 years', the abnormality criteria were '>180 ms' (Abn A) and '>25% increase from Baseline' value (Abn B). For the age range, '>=12 years - <17 years', the abnormality criteria were '>200 ms' (Abn C) and '>25% increase from Baseline' value (Abn D). For age range, '>=17 years', the abnormality criteria were treatment-emergent values above '>200 ms' (Abn E), '>220 ms' (Abn F), or '>250 ms' (Abn G).
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (QRS Interval) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA ECG results of QRS interval were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '3 years -<12 years', the abnormality criteria were '>100 ms' (Abn A) and '>25% increase from Baseline' value (Abn B). For the age range, '>=12 years - <17 years', the abnormality criteria were '>110 ms' (Abn C) and '>25% increase from Baseline' (Abn D). For age range, '>=17 years', the abnormality criteria were treatment-emergent values above '>100 ms' (Abn E), '>120 ms' (Abn F), or '>140 ms' (Abn G).
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in 12-lead ECG Parameter (Heart Rate Interval) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA ECG results of Heart rate interval were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '3 years -<12 years', the abnormality criteria were '<60 beats per minute (bpm)' (Abn A) and '>130 bpm' (Abn B). For the age range, '>=12 years', the abnormality criteria were '<50 bpm' (Abn C) and '>120 bpm' (Abn D).
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Pulse Rate) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA vital signs results of Pulse rate were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '3 years -<12 years', the abnormality criteria were '<60 bpm' (Low) and '>130 bpm' (High). For the age range, '12 years - <17 years', the abnormality criteria were '<=50 bpm' (Low) and '>=120 bpm' (High). For the age range, '>=17 years', the abnormality criteria were '<=50 bpm and a decrease from Baseline of >=15 bpm' (Low A), '>=120 bpm and an increase from Baseline of >=15 bpm' (High A), '<60 bpm' (Low B) and '>100 bpm' (High B). The Pulse rate was reported as per positions such as 'Supine 3 minute (Sup 3 min)', 'Standing 1 minute' (Std 1 min), and 'Standing 3 minute' (Std 3 min).
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Systolic Blood Pressure) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values of Systolic Blood Pressure (BP) results were those that were observed post- BL during the Treatment Period but not present at Baseline. For the age range, '3 years -<12 years', the abnormality criteria were '<80 millimeters of mercury (mmHg)' (Low) and '>140 mmHg' (High). For the age range, '>=12 years - <17 years', the abnormality criteria were '<90 mmHg' (Low) and '>160 mmHg' (High). For the age range, '>=17 years', the abnormality criteria were '<=90 mmHg and decrease from Baseline of >=20 mmHg' (Low A), '>=180 mmHg and increase from Baseline of >=20' mmHg (High A), '<90 mmHg' (Low B), '>140 mmHg (High B), and '>160 mmHg' (High C). Systolic BP were reported as per positions such as 'Sup 3 min', 'Std 1 min, and 'Std 3 min'.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Diastolic Blood Pressure) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values of Diastolic BP results were those that are observed post- BL during the Treatment Period but not present at Baseline. For the age range, '3 years -<12 years', the abnormality criteria were '<50 mmHg' (Low) and '>80 mmHg' (High), '>=12 years - <17 years', the abnormality criteria were '<=50 mmHg' (Low) and '>=105 mmHg' (High), and '>=17 years', the abnormality criteria were '<=50 mmHg and decrease from Baseline of >=15 mmHg' (Low A), '>=105 mmHg and increase from Baseline of >=15' mmHg (High A), '<50 mmHg' (Low B), '>90 mmHg' (High B), and '>100 mmHg' (High C). Diastolic BP were reported as per positions such as 'Sup 3 min', 'Std 1 min, and 'Std 3 min'.
• Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Body Weight) [ Time Frame: During the study (up to approximately 5 years) ]
  TEMA values are defined in the SAP as significant deviations from the expected range of age-appropriate values. TEMA vital signs parameter results were those that are observed post- BL during the Treatment Period but not present at Baseline. For the age range, '1 month - <17 years', the abnormality criteria were '<3% of normal body weight' in Kilograms (kg) or '>97% of normal body weight' in kgs. Here, '<3% of normal' is presented as 'Low' and '>97% of normal' is presented as 'High'. For the age range '>=17 years', the abnormality criteria were 'Increase/decrease of >=10%' body weight in kgs (presented as Inc/Dec A) or 'Increase/decrease of >=7%' body weight in kgs (presented as Inc/Dec B).
• Percent Change in Primary Generalized Tonic-clonic Seizure (PGTCS) Frequency Per 28 Days From Combined Baseline [ Time Frame: From Combined Baseline until end of Treatment Period (up to approximately 5 years) ]
  The 28-day PGTCS frequency during the relative period was subtracted from the 28-day Combined Baseline PGTCS frequency and the result was divided by 28-day Combined Baseline PGTCS frequency and the result was then multiplied by 100 to get percent change in PGTCS frequency per 28 days from Combined Baseline Period (CB) to the appropriate analysis Period. The CB was defined as the combined 12-week Historical Baseline and 4-week Prospective Baseline periods immediately prior to randomization in the study SP0982 or prior to Visit 1 (first dose) if direct enrollers in EP0012.

Original Secondary Outcome Measures (submitted: March 31, 2015)

Percent change in Primary Generalized Tonic-clonic (PGTC) seizure frequency per 28 days from Baseline [ Time Frame: 28 days from Baseline ]

Percent change in PGTC seizure frequency per 28 days from Baseline, where Baseline is defined as the 12-week Historical Baseline and 4-week Prospective Baseline periods immediately prior to randomization in the parent study (SP0982).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Lacosamide as Additional Therapy in Patients Suffering From Epileptic Tonic-Clonic Seizures
• Official Title: An Open-label, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy
• Brief Summary: Assessment of long-term safety and efficacy of oral lacosamide (LCM) as an adjunctive therapy for uncontrolled primary generalized tonic-clonic seizures (PGTCS) in subjects >= 4 years of age with idiopathic generalized epilepsy (IGE). This study will enroll subjects from the LCM SP0982 [NCT02408523] study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsy

Intervention

• Drug: Lacosamide Tablet
  • Active substance: Lacosamide
  • Pharmaceutical form: Tablet
  • Concentration: 50 mg and 100 mg
  • Route of Administration: Oral administration
  Other Names:

  • Vimpat
  • LCM
• Drug: Lacosamide Oral Solution
  • Active substance: Lacosamide
  • Pharmaceutical form: Oral solution
  • Concentration: 10 mg/ml
  • Route of Administration: Oral administration
  Other Names:

  • Vimpat
  • LCM

Study Arms

Experimental: Lacosamide

Start dose

SP0982 completers at V1:

• LCM 10 mg/kg/day for pediatric subjects weighing <30 kg
• LCM 8 mg/kg/day for pediatric subjects weighing ≥ 30kg to <50 kg
• LCM 400 mg/day (200 mg bid) for adult subjects (≥18 years of age) or pediatric subjects weighing ≥50 kg

SP0982 Baseline failures at V1:

• LCM 2 mg/kg/day for pediatric subjects weighing <50 kg
• LCM 100 mg/day (50 mg bid) for adult subjects (≥18 years of age) or pediatric subjects weighing ≥50 kg

Oral solution (pediatric subjects <50 kg):

• Minimum LCM dose: 4 mg/kg/day
• Maximum LCM dose: 12 mg/kg/day

Tablets (pediatric subjects ≥50kg):

• Minimum LCM dose: 200 mg/day
• Minimum LCM dose: 600 mg/day

Tablets (adult subjects):

• Minimum LCM dose: 200 mg/day
• Maximum LCM dose: 800 mg/day

Interventions:

• Drug: Lacosamide Tablet
• Drug: Lacosamide Oral Solution

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 21, 2019): 239
• Original Estimated Enrollment (submitted: March 31, 2015): 200
• Actual Study Completion Date: March 30, 2023
• Actual Primary Completion Date: March 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

- Subject must have completed or be an eligible Baseline failure from the parent study (SP0982 [NCT02408523]). Note: Other subjects screened for SP0982 may be considered for roll-over to EP0012 if the investigator considers that the subject could benefit from treatment with open-label lacosamide (LCM) and based on prior discussion with and approval from the UCB Study Physician or representative

Exclusion Criteria:

• Subject is receiving any investigational drugs or using any experimental devices in addition to lacosamide (LCM)
• Subject meets the withdrawal criteria for SP0982 or is experiencing an ongoing serious adverse event (SAE)
• Subject has an active suicidal ideation as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the "Since Last Visit" version of the Columbia-Suicide Severity Rating Scale (C-SSRS)
• Subject has >=2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin <35%). For all subjects who entered EP0012 directly with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic Case Report form (eCRF). Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated once for confirmation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Bulgaria, China, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Taiwan, United States
• Removed Location Countries: Belgium, Czech Republic, Turkey

Administrative Information

• NCT Number: NCT02408549
• Other Study ID Numbers: EP0012; 2012-001770-29 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• URL: https://www.Vivli.org

• Current Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: UCB BIOSCIENCES, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; 001 844 599 2273

• PRS Account: UCB Pharma
• Verification Date: November 2023