Safety and Efficacy of Lacosamide as Additional Therapy in Patients Suffering From Epileptic Tonic-Clonic Seizures
- Conditions
- Epilepsy
- Interventions
- Registration Number
- NCT02408549
- Lead Sponsor
- UCB BIOSCIENCES, Inc.
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 239
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lacosamide Lacosamide Oral Solution 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 Lacosamide Lacosamide Tablet 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
- Primary Outcome Measures
Name Time Method 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) 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 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) 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 >75% in Days With Absence Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) 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 Treatment-emergent Adverse Events (TEAEs) Over the Duration of the Treatment Period 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 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 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) 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 >50% to 75% in Days With Absence Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) 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 up to 25% in Days With Myoclonic Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) 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 >50% to 75% in Days With Myoclonic Seizures Per 28 Days During the Treatment Period as Compared to the Prospective Baseline (of Study SP0982) 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) 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 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 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.
- Secondary Outcome Measures
Name Time Method Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Calcium) 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) 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 Hematology Parameters (Hemoglobin) 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 (Basophils Absolute) 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) 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) 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 ) 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) 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 Hematology Parameters (Hematocrit) 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) 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) 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) 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 Serum Chemistry Parameters (Potassium) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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 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.
Trial Locations
- Locations (87)
EP0012 8
🇺🇸Santa Monica, California, United States
Ep0012 651
🇵🇱Katowice, Poland
Ep0012 650
🇵🇱Warszawa, Poland
Ep0012 161
🇲🇽Guadalajara, Mexico
Ep0012 960
🇨🇳Taipei, Taiwan
Ep0012 972
🇨🇳Shanghai, China
Ep0012 303
🇩🇪Erlangen, Germany
Ep0012 314
🇩🇪Freiburg, Germany
Ep0012 311
🇩🇪Marburg, Germany
Ep0012 552
🇨🇿Zlin, Czechia
Ep0012 252
🇫🇷Lille Cedex, France
Ep0012 38
🇺🇸San Antonio, Texas, United States
Ep0012 500
🇧🇬Blagoevgrad, Bulgaria
Ep0012 31
🇺🇸Colorado Springs, Colorado, United States
Ep0012 42
🇺🇸Loxahatchee Groves, Florida, United States
Ep0012 21
🇺🇸Peoria, Illinois, United States
Ep0012 255
🇫🇷Bron Cedex, France
Ep0012 27
🇺🇸Renton, Washington, United States
Ep0012 23
🇺🇸Madison, Wisconsin, United States
Ep0012 181
🇧🇷Curitiba, Brazil
Ep0012 501
🇧🇬Sofia, Bulgaria
EP0012 2
🇺🇸Port Charlotte, Florida, United States
Ep0012 985
🇦🇺Heidelberg, Australia
Ep0012 180
🇧🇷Florianopolis, Brazil
Ep0012 981
🇦🇺Parkville, Australia
Ep0012 53
🇺🇸Austin, Texas, United States
Ep0012 185
🇧🇷Porto Alegre, Brazil
Ep0012 188
🇧🇷Rio de Janeiro, Brazil
Ep0012 183
🇧🇷Sao Paulo, Brazil
Ep0012 553
🇨🇿Prague, Czechia
Ep0012 600
🇭🇺Budapest, Hungary
Ep0012 451
🇵🇹Lisboa, Portugal
Ep0012 900
🇯🇵Sapporo-city, Japan
Ep0012 914
🇯🇵Kodaira-city, Japan
Ep0012 902
🇯🇵Hiroshima, Japan
Ep0012 851
🇮🇱Tel Hashomer, Israel
Ep0012 961
🇨🇳Taichung, Taiwan
Ep0012 407
🇪🇸Madrid, Spain
Ep0012 406
🇪🇸Cordoba, Spain
Ep0012 403
🇪🇸Sevilla, Spain
Ep0012 901
🇯🇵Niigata-city, Japan
EP0012 5
🇺🇸Little Rock, Arkansas, United States
Ep0012 15
🇺🇸Boise, Idaho, United States
Ep0012 980
🇦🇺Chatswood, Australia
Ep0012 43
🇺🇸New York, New York, United States
Ep0012 13
🇺🇸Panama City, Florida, United States
Ep0012 25
🇺🇸Golden Valley, Minnesota, United States
Ep0012 50
🇺🇸Greenville, Texas, United States
Ep0012 34
🇺🇸Houston, Texas, United States
Ep0012 986
🇦🇺Melbourne, Australia
Ep0012 556
🇨🇿Praha 11, Czechia
Ep0012 971
🇨🇳Beijing, China
Ep0012 976
🇨🇳Changchun, China
Ep0012 550
🇨🇿Ostrava- Poruba, Czechia
Ep0012 251
🇫🇷Nancy, France
Ep0012 603
🇭🇺Szeged, Hungary
Ep0012 850
🇮🇱Rehovot, Israel
Ep0012 351
🇮🇹Torino, Italy
Ep0012 906
🇯🇵Fukuoka-shi, Japan
Ep0012 903
🇯🇵Hamamatsu, Japan
Ep0012 910
🇯🇵Gifu, Japan
Ep0012 912
🇯🇵Kagoshima-city, Japan
Ep0012 909
🇯🇵Kokubunji-shi, Japan
Ep0012 911
🇯🇵Omura-shi, Japan
Ep0012 908
🇯🇵Shinjuku-ku, Japan
Ep0012 657
🇵🇱Czestochowa, Poland
Ep0012 655
🇵🇱Gdansk, Poland
Ep0012 652
🇵🇱Gliwice, Poland
Ep0012 653
🇵🇱Katowice, Poland
Ep0012 654
🇵🇱Katowice, Poland
Ep0012 656
🇵🇱Tyniec Maly, Poland
Ep0012 659
🇵🇱Warszawa, Poland
Ep0012 704
🇷🇴Iasi, Romania
Ep0012 700
🇷🇴Timisoara, Romania
Ep0012 757
🇷🇺Ekaterinburg, Russian Federation
Ep0012 750
🇷🇺Kazan, Russian Federation
Ep0012 756
🇷🇺Saint Petersburg, Russian Federation
Ep0012 823
🇸🇰Hlohovec, Slovakia
Ep0012 758
🇷🇺Pyatigorsk, Russian Federation
Ep0012 755
🇷🇺St. Petersburg, Russian Federation
Ep0012 821
🇸🇰Bardejov, Slovakia
Ep0012 752
🇷🇺Samara, Russian Federation
Ep0012 402
🇪🇸Barcelona, Spain
Ep0012 944
🇰🇷Seoul, Korea, Republic of
Ep0012 186
🇧🇷Passo Fundo, Brazil
Ep0012 940
🇰🇷Daegu, Korea, Republic of
Ep0012 941
🇰🇷Seoul, Korea, Republic of