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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 239
- 试验地点
- 87
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Lacosamide Tablet (Drug)
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
干预措施: Lacosamide Oral Solution (Drug)
结局指标
主要结局
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)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Calcium)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Sodium)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Hemoglobin)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Basophils Absolute)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Eosinophils Absolute)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Lymphocytes Absolute)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Monocytes Absolute )(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Neutrophils Absolute)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Hematocrit)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Platelets)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Hematology Parameters (Erythrocytes)(During 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))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Potassium)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Chloride)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Bicarbonate)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Creatinine)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Aspartate Aminotransferase)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Alanine Aminotransferase)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Chemistry Parameters (Total Bilirubin)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Alkaline Phosphatase)(During the study (up to approximately 5 years))
- 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))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Glucose)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Albumin)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Total Protein)(During the study (up to approximately 5 years))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Serum Chemistry Parameters (Phosphate)(During the study (up to approximately 5 years))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Pulse Rate)(During the study (up to approximately 5 years))
- 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))
- 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))
- Percentage of Study Participants With Treatment-emergent Marked Abnormalities (TEMAs) in Vital Sign Measurements (Body Weight)(During the study (up to approximately 5 years))
- 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))