This is a two-part, multicenter, double-blind, parallel-group, placebo controlled study to evaluate the effect of ZX008 when used as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with Lennox-Gastaut syndrome (LGS).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
296
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride. The product is sugar free and is intended to be compatible with a Ketogenic Diet.
Placebo will be administered twice a day (BID) in equally divided doses.
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2.
Time frame: From Part 2 Baseline until end of the OLE Period (up to 72 months)
Part 2: Percentage of Participants With Serious TEAEs
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
Time frame: From Part 2 Baseline until end of the OLE Period (up to 72 months)
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/Day Group Compared to the Placebo Group
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Tucson, Arizona, United States
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Los Angeles, California, United States
Ep0214 101
San Francisco, California, United States
Ep0214 103
Aurora, Colorado, United States
Ep0214 149
Washington D.C., District of Columbia, United States
Ep0214 115
Gulf Breeze, Florida, United States
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Miami, Florida, United States
Ep0214 141
Orlando, Florida, United States
Ep0214 121
Orlando, Florida, United States
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Atlanta, Georgia, United States
...and 62 more locations
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieve a >=50% Reduction From Baseline in the Frequency of Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. Participants who achieved a \>=50% reduction from Baseline in the DSF, ie, a decrease in DSF of at least 50 percentage points per 28 days during Titration and Maintenance Period.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieve Improvement (Minimally, Much or Very Much Improved) in the CGI-I Scale as Assessed by Principal Investigator Comparing ZX008 0.8 and 0.2 mg/kg/Day Groups Independently Versus Placebo
Clinical Global Impression - Improvement (CGI-I) scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Time frame: At Day 99 (Visit 12)
Part 1: Percent Change From Baseline in Frequency of All Seizures That Typically Result in Drops in T+M, Whether ESC-confirmed as Drop or Not in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Seizures that typically result in drops included all: generalized tonic-clonic seizures \[GTC\], secondarily generalized tonic-clonic \[SGTC\], tonic seizures \[TS\], atonic seizures \[AS\], and tonic/atonic seizures \[TA\], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures \[CS\], hemiclonic seizures \[HS\], and focal seizures \[FS\] with clearly observable signs.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) Between Baseline and the Maintenance Period
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of Seizures That Typically Result in Drops in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC,TS, AS, TA, CS, HS, and FS with clearly observable signs.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in Frequency of Countable Seizures That do Not Result in Drops (ESC Confirmed)
Non-drop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each participant as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
Countable non-motor seizures include: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Change From Baseline in Number of Seizure-free Days During T+M and M Period
A day with no seizures leading to a drop was defined as a day for which electronic (e) diary data were available and no drop seizures were reported. The total number of drop seizure-free days was calculated per 28 days for Baseline and for T+M.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Duration of Longest Interval (Days) Between Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
The longest interval between seizures leading to drops were obtained from the eDiary entries in Titration and Maintenance Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved, 2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Time frame: At Days 15, 43, 71 and 99
Part 1: Percentage of Participants With TEAEs
Adverse events were defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A TEAE in Part 1 was defined as any AE that, based on start date information, occurred after the first dose of study drug in Part 1, but not on or after the first dose of study drug in Part 2.
Time frame: Baseline up to 14 weeks + Taper/Transition (2 weeks)
Part 1: Percentage of Participants With Serious TEAEs
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
Time frame: Baseline up to 14 weeks + Taper/Transition (2 weeks)
Part 1: Maximum Observed Plasma Concentration of Fenfluramine and Norfenfluramine Determined Directly From the Concentration Time Profile [Cmax] at Steady State
Cmax is the maximum plasma concentration determined directly from the concentration time profile.
Time frame: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 1: Minimum Observed Plasma Concentration of Fenfluramine and Norfenfluramine at Steady State Determined Directly From the Concentration-time Profile [Cmin] at Steady State
Cmin is the minimum plasma concentration determined directly from the concentration-time profile.
Time frame: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 1: Area Under the Concentration-time Curve of Fenfluramine and Norfenfluramine From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State
AUC0-24 is the area under the concentration-time curve from time 0 to 24 hours.
Time frame: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 2: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) in OLE Period
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Seizures That Typically Result in Drops Between Baseline and the OLE Period Whether ESC Confirmed as Drop or Not
Seizures that typically result in drops included all: generalized tonic-clonic seizures \[GTC\], secondarily generalized tonic-clonic \[SGTC\], tonic seizures \[TS\], atonic seizures \[AS\], and tonic/atonic seizures \[TA\], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in OLE Period
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures \[CS\], hemiclonic seizures \[HS\], and focal seizures \[FS\] with clearly observable signs.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in the Frequency of All Countable Non-motor Seizures in OLE Period
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Countable Seizures (ESC Confirmed or Not) in OLE Period
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in the Frequency of All Countable Seizures That Did Not Result in Drops (ESC Confirmed) in OLE Period
Nondrop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each subject as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in Number of Seizure-free Days Per 28 Days (ESC Confirmed) in OLE Period
A day with no seizures leading to a drop was defined as a day for which ediary data were available and no drop seizures were reported.
Time frame: From Part 2 Baseline until end of OLE Period (up to 72 months)
Part 2: Change From Baseline in Duration of Longest Interval Between Seizures That Result in Drops (ESC Confirmed) in OLE Period
The longest interval between seizures leading to drops were obtained from the eDiary entries in OLE Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
Time frame: From Part 2 Baseline until end of the OLE Period (up to 72 months)
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Time frame: At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Time frame: At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)