A Study to Investigate the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Children and Adults With Epileptic Encephalopathy Including Dravet Syndrome and Lennox-Gastaut Syndrome

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can, therefore, be 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. TEAEs were defined as AE that began on or after the first day of treatment with ZX008 in Study EP0215 (ZX008-1900) (NCT03936777) or that occurred prior to first ZX008 treatment in Study EP0215 (ZX008-1900) but increased in severity after treatment in Study EP0215 (ZX008-1900) began. Events recorded at Follow-up/Cardiac Follow-up were considered treatment-emergent. The percentage of participants was rounded to one decimal place.

Time frame: From First dose of ZX008 (in study EP0215 [ZX008-1900]) to Cardiac Follow-up after ZX008 treatment (Up to 6 Years, 17 Days)

Population: Safety analysis set consisted of participants who received at least one dose of ZX008 during the open label extension.

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Behavior is one of the domains assessed by the CGI-I scale. The CGI-I is 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; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of behavior was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Time frame: Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The mITT analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the OLE in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Behavior is one of the domains assessed by the CGI-I scale. The CGI-I is 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; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of behavior was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Time frame: Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The mITT analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the OLE in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Cognitive function is one of the domains assessed by the CGI-I scale. The CGI-I is 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; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of cognition was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Time frame: Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The mITT analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the OLE in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Cognitive function is one of the domains assessed by the CGI-I scale. The CGI-I is 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; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of cognition was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Time frame: Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The modified Intent-to-Treat (mITT) analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the open-label extension (OLE) in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Global function is one of the domains assessed by the CGI-I scale. The CGI-I is 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; 7=Very much worse, where higher score indicates worse outcome. The global CGI-I assessment was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Time frame: Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The mITT analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the OLE in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

The Clinical Global Impression-Improvement (CGI-I) scale is used to assess the severity of illness and global improvement in patients. Global function is one of the domains assessed by the CGI-I scale. The CGI-I is 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; 7=Very much worse, where higher score indicates worse outcome. The global CGI-I assessment was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Time frame: Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The mITT analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the OLE in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Motor abilities is one of the domains assessed by the CGI-I scale. The CGI-I is 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; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of motor abilities was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Time frame: Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The mITT analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the OLE in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Motor abilities function is one of the domains assessed by the CGI-I scale. The CGI-I is 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; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of motor abilities was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Time frame: Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The mITT analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the OLE in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

The change in seizure burden from the previous visit was assessed by the investigator using following categories: \<25%, ≥25%, ≥50%, ≥75%, 100% (i.e., seizure-free) improvement. Improvement in seizure burden at Baseline was based on comparison with the participant's last visit in the feeder studies (ZX008-1601, ZX008-1503, and ZX008-1602). Number of participants in each of the 5 categories is reported for each visit as compared to last visit.

Time frame: Baseline (Day 1), Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Population: The mITT analysis set consisted of all participants who received at least 1 dose of ZX008 and had at least one valid efficacy assessment during the OLE in the study EP0215 (ZX008-1900). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.