An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution in Children and Young Adults With Dravet Syndrome

• ClinicalTrials.gov Identifier: NCT02823145
• Recruitment Status: Completed
• First Posted: July 6, 2016
• Results First Posted: September 25, 2023
• Last Update Posted: September 25, 2023
• Sponsor: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
• Information provided by (Responsible Party): UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Dravet Syndrome
• Intervention: Drug: ZX008 (Fenfluramine Hydrochloride)
• Enrollment: 375

Participant Flow

Recruitment Details	The study started to enroll participants in Jun 2016 and concluded in Jan 2023. Participants who completed 14 weeks treatment in any of the core studies ZX008-1501/ZX008-1502 (NCT02682927), or ZX008-1504 (NCT02926898) Cohort 2, or completed ZX008-1504 Cohort 1 study, and de novo participants were eligible to participate in this study.
Pre-assignment Details	The Participant Flow refers to the Safety (SAF) Population.

Arm/Group Title	Not Treated	Any ZX008 Open Label Dose
Arm/Group Description	Participant (de novo) signed the informed consent form (ICF) but never received any study medication during the study.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Period Title: Enrollment
Started	1	374
Completed	0	374
Not Completed	1	0
Reason Not Completed
Other	1	0
Period Title: Treatment
Started	0	374
Completed	0	49
Not Completed	0	325
Reason Not Completed
Adverse Event	0	11
Death	0	3
Family Decision	0	1
IP approved and subject moved to commercial drug	0	1
Lack of Efficacy	0	48
Non-Compliance With E-Diary	0	1
Physician Decision	0	2
Subject has transitioned to study 1900 OLE study	0	225
Subject needed to take prohibited medication	0	1
Subject transferred to direct access programme	0	1
Switching to commercially available drug	0	11
Transitioned to commercial supply of medication	0	1
Withdrawal By Caregiver	0	1
Withdrawal by sponsor due to lack of compliance	0	1
Withdrawal by Subject	0	16
Reason unknown	0	1

Baseline Characteristics

Arm/Group Title		Any ZX008 Open Label Dose
Arm/Group Description		Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Baseline Participants		374
Baseline Analysis Population Description		Baseline characteristics refers to the Safety (SAF) population which included all enrolled participants who received at least one dose of ZX008 during the open label extension (OLE). As pre-specified in the SAP, participant Demographics and Baseline Characteristics were summarized for the safety population.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	374 participants
		10.3 (6.12)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	374 participants
	<6 years	92 24.6%
	6-18 years	250 66.8%
	>18 years	32 8.6%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	374 participants
	Female	172 46.0%
	Male	202 54.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	374 participants
	White	275 73.5%
	Black or African American	5 1.3%
	Asian	31 8.3%
	American Indian or Alaska Native	2 0.5%
	Other	17 4.5%
	Not Reported	44 11.8%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	374 participants
	Hispanic or Latino	44 11.8%
	Not Hispanic or Latino	267 71.4%
	Not Reported	55 14.7%
	Unknown	8 2.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period
Description	Treatment-emergent adverse events (TEAE) were defined as any AEs that based on start date information occurs after the first intake of study treatment.
Time Frame	From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)

Outcome Measure Data

Analysis Population Description

Safety (SAF) population included all enrolled participants who received at least one dose of ZX008 during the OLE.

Arm/Group Title	Any ZX008 Open Label Dose
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Participants Analyzed	374
Measure Type: Number; Unit of Measure: percentage of participants
	98.1

2. Primary Outcome

Title	Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the OLE Treatment Period
Description	A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. Percentage of participants with TEAEs leading to withdrawal from IMP during OLE Treatment Period were reported.
Time Frame	From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)

Outcome Measure Data

Analysis Population Description

Safety (SAF) population included all enrolled participants who received at least one dose of ZX008 during the OLE.

Arm/Group Title	Any ZX008 Open Label Dose
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Participants Analyzed	374
Measure Type: Number; Unit of Measure: percentage of participants
	3.5

3. Primary Outcome

Title	Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) During the OLE Treatment Period
Description	Serious Adverse event (SAE) was defined as any untoward medical occurrence that at any dose: • results in death, • is life-threatening threatening, • results in initial inpatient hospitalization or prolongation of hospitalization, •results in persistent or significant disability or incapacity, • results in a congenital anomaly/birth defect, • results in any medically significant event that did not meet any of the other 5 SAE criteria, but which was judged by a physician to potentially jeopardize the participant or require medical or surgical intervention to prevent one of the above outcomes listed as an SAE criterion.
Time Frame	From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)

Outcome Measure Data

Analysis Population Description

Safety (SAF) population included all enrolled participants who received at least one dose of ZX008 during the OLE.

Arm/Group Title	Any ZX008 Open Label Dose
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Participants Analyzed	374
Measure Type: Number; Unit of Measure: percentage of participants
	26.5

4. Secondary Outcome

Title	Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Day 1 to End of Study (EOS) Visit (Month 42) in the OLE Treatment Period
Description	Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies (ZX008-1501/ZX008-1502, and ZX008-1504 Cohort 2). Participants in 1504- Cohort 1 and de novo participants (who entered 1503 without having been in any of the core studies) did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Day 1 to EOS was divided by the total number of days from Day 1 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day convulsive seizure frequency (CSF). The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant.
Time Frame	From Day 1 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE.

Arm/Group Title	Any ZX008 Open Label Dose
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Participants Analyzed	324
Median (Full Range); Unit of Measure: seizure frequency per 28 days
	-6.67; (-1757.8 to 751.3)

5. Secondary Outcome

Title	Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Month 2 to EOS (Month 42) in the OLE Treatment Period
Description	Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies. Participants in 1504-Cohort 1 and de novo participants did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Month 2 to EOS was divided by the total number of days from Month 2 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF. The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant.
Time Frame	From Month 2 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)

Outcome Measure Data

Analysis Population Description

mITT population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE. Here, number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Any ZX008 Open Label Dose
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Participants Analyzed	323
Median (Full Range); Unit of Measure: seizure frequency per 28 days
	-7.04; (-1986.9 to 816.4)

6. Secondary Outcome

Title	Convulsive Seizure Frequency (CSF) Per 28 Days During the OLE Treatment Period (to Month 36)
Description	Monthly (28 day) CSF was based on electronic diary data obtained for each participant. The total number of convulsive seizures in the ith interval (CSF in OLE, where, i=1, 2, 3, … , 14 ) was divided by the total number of days in the ith interval with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF of OLE.
Time Frame	At Month 1, Month 2, Month 3, Month 4-6, Month 7-9, Month 10-12, Month 13-15, Month 16-18, Month 19-21, Month 22-24, Month 25-27, Month 28-30, Month 31-33, and Month 34-36

Outcome Measure Data

Analysis Population Description

mITT population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE. Here, number analyzed signifies participants who were evaluable at specified time points.

Arm/Group Title		Any ZX008 Open Label Dose
Arm/Group Description:		Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Participants Analyzed		324
Median (Full Range); Unit of Measure: seizure frequency per 28 days
Month 1	Number Analyzed	324 participants
		6.53; (0.0 to 4876.9)
Month 2	Number Analyzed	323 participants
		4.67; (0.0 to 3392.7)
Month 3	Number Analyzed	320 participants
		4.67; (0.0 to 2593.7)
Month 4-6	Number Analyzed	316 participants
		4.36; (0.0 to 1725.5)
Month 7-9	Number Analyzed	299 participants
		3.82; (0.0 to 310.8)
Month 10-12	Number Analyzed	284 participants
		4.04; (0.0 to 362.4)
Month 13-15	Number Analyzed	280 participants
		3.11; (0.0 to 215.0)
Month 16-18	Number Analyzed	262 participants
		3.42; (0.0 to 243.3)
Month 19-21	Number Analyzed	247 participants
		3.42; (0.0 to 372.4)
Month 22-24	Number Analyzed	234 participants
		2.80; (0.0 to 489.5)
Month 25-27	Number Analyzed	187 participants
		2.80; (0.0 to 747.3)
Month 28-30	Number Analyzed	151 participants
		2.80; (0.0 to 242.5)
Month 31-33	Number Analyzed	116 participants
		3.21; (0.0 to 224.0)
Month 34-36	Number Analyzed	73 participants
		2.74; (0.0 to 56.0)

7. Secondary Outcome

Title	Convulsive Seizure Frequency (CSF) by Mean Daily Dose During the Overall OLE Treatment Period
Description	Convulsive seizure frequency over time, reported as per 28 days was analyzed by the actual dose administered. Participants were grouped into low (0.2 to <0.4 mg/kg), medium (0.4 to <0.6 mg/kg), and high dose (>0.6 mg/kg) groups depending on their mean daily doses of ZX008 during the OLE Treatment period. 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. The convulsive seizure frequency was calculated from all available data collected.
Time Frame	From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)

Outcome Measure Data

Analysis Population Description

mITT population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE. Here, number analyzed represents the number of participants categorized by mean daily dose.

Arm/Group Title		Any ZX008 Open Label Dose
Arm/Group Description:		Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Participants Analyzed		324
Median (Full Range); Unit of Measure: seizure frequency per 28 days
ZX008 Low Dose (0 - <0.4 mg/kg/day)	Number Analyzed	90 participants
		3.94; (0.0 to 2215.3)
ZX008 Medium Dose (0.4 - <0.6 mg/kg/day)	Number Analyzed	113 participants
		4.80; (0.0 to 113.6)
ZX008 High Dose (>=0.6 mg/kg/day)	Number Analyzed	121 participants
		6.00; (0.1 to 942.8)

8. Secondary Outcome

Title	Percentage of Participants With Changes in Antiepileptic Drug (AED) Medications During First 6 Months of OLE Treatment Period
Description	Participants in the study were required to be on stable background therapy for the first 6 months of treatment, after which background AEDs could be reduced or withdrawn so long as one background AED remained. The percentage of participants who had changes in dose or type of concomitant AED medications during the first, second, third, fourth, fifth, and sixth months were analyzed and reported.
Time Frame	At Month 1, 2, 3, 4 , 5, and 6 of OLE Treatment Period

Outcome Measure Data

Analysis Population Description

mITT population included all enrolled participants who received at least one dose of ZX008 and had at least 1 month of valid seizure data during the OLE.

Arm/Group Title	Any ZX008 Open Label Dose
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
Overall Number of Participants Analyzed	324
Measure Type: Number; Unit of Measure: percentage of participants
OLE Month 1	5.2
OLE Month 2	7.1
OLE Month 3	7.4
OLE Month 4	8.3
OLE Month 5	6.8
OLE Month 6	9.6

Adverse Events

Time Frame	From Day 1 up to 42 months
Adverse Event Reporting Description	A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. The Safety (SAF) population was the set of all enrolled subjects who received at least one dose of ZX008 during the OLE. As pre-specified in the SAP, safety analyses were performed on the SAF Population.
Arm/Group Title	Any ZX008 Open Label Dose
Arm/Group Description	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), in equally divided doses with food for 1 month. After 1 month, investigator might have adjusted the dose of each participant based on effectiveness and tolerability. Participants who were not receiving concomitant stiripentol, dose changes should be made in increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day but not to exceed total dose of 30 mg/day for 42 months of OLE Period. Participants who were receiving concomitant stiripentol, the first dose change was 0.4 mg/kg/day and the final dose change was to 0.5 mg/kg/day, but not to exceed 20 mg/day for 42 months of OLE Period.
All-Cause Mortality
	Any ZX008 Open Label Dose
	Affected / at Risk (%)
Total	3/374 (0.80%)
Serious Adverse Events
	Any ZX008 Open Label Dose
	Affected / at Risk (%)	# Events
Total	99/374 (26.47%)
Cardiac disorders
Atrioventricular block second degree * 1	1/374 (0.27%)	1
Supraventricular tachycardia * 1	1/374 (0.27%)	1
Gastrointestinal disorders
Colitis * 1	1/374 (0.27%)	1
Constipation * 1	2/374 (0.53%)	2
Diarrhoea haemorrhagic * 1	1/374 (0.27%)	1
Duodenal perforation * 1	1/374 (0.27%)	1
Dysphagia * 1	2/374 (0.53%)	2
Enterovesical fistula * 1	1/374 (0.27%)	1
Haematemesis * 1	1/374 (0.27%)	1
Pancreatitis * 1	1/374 (0.27%)	1
Tooth disorder * 1	1/374 (0.27%)	1
General disorders
Abasia * 1	1/374 (0.27%)	1
Fatigue * 1	1/374 (0.27%)	1
Hypothermia * 1	1/374 (0.27%)	1
Impaired healing * 1	1/374 (0.27%)	1
Sudden unexplained death in epilepsy * 1	3/374 (0.80%)	3
Infections and infestations
Atypical pneumonia * 1	1/374 (0.27%)	1
Bronchitis * 1	1/374 (0.27%)	1
Bronchitis viral * 1	1/374 (0.27%)	1
Cellulitis * 1	2/374 (0.53%)	2
Enterovirus infection * 1	1/374 (0.27%)	1
Epididymitis * 1	1/374 (0.27%)	1
Epstein-Barr virus infection * 1	1/374 (0.27%)	1
Gastroenteritis * 1	3/374 (0.80%)	3
Gastroenteritis viral * 1	1/374 (0.27%)	1
Helicobacter infection * 1	1/374 (0.27%)	1
Infectious mononucleosis * 1	1/374 (0.27%)	1
Influenza * 1	7/374 (1.87%)	8
Lower respiratory tract infection * 1	3/374 (0.80%)	3
Lung infection * 1	1/374 (0.27%)	1
Otitis media acute * 1	1/374 (0.27%)	1
Pharyngitis * 1	1/374 (0.27%)	1
Pneumonia * 1	12/374 (3.21%)	15
Postoperative wound infection * 1	2/374 (0.53%)	2
Respiratory syncytial virus infection * 1	1/374 (0.27%)	1
Rhinovirus infection * 1	1/374 (0.27%)	2
Sepsis * 1	3/374 (0.80%)	4
Tonsillitis * 1	1/374 (0.27%)	1
Upper respiratory tract infection * 1	1/374 (0.27%)	1
Urinary tract infection * 1	1/374 (0.27%)	1
Varicella * 1	1/374 (0.27%)	1
Viral infection * 1	5/374 (1.34%)	5
Viral pharyngitis * 1	1/374 (0.27%)	1
Viral upper respiratory tract infection * 1	1/374 (0.27%)	1
Injury, poisoning and procedural complications
Abdominal injury * 1	1/374 (0.27%)	1
Ankle fracture * 1	1/374 (0.27%)	1
Cervical vertebral fracture * 1	1/374 (0.27%)	1
Concussion * 1	1/374 (0.27%)	1
Drug dose omission * 1	1/374 (0.27%)	1
Femur fracture * 1	1/374 (0.27%)	1
Foreign body aspiration * 1	1/374 (0.27%)	1
Hand fracture * 1	1/374 (0.27%)	1
Head injury * 1	2/374 (0.53%)	2
Lower limb fracture * 1	1/374 (0.27%)	1
Near drowning * 1	1/374 (0.27%)	1
Investigations
Blood glucose decreased * 1	1/374 (0.27%)	1
Heart rate decreased * 1	1/374 (0.27%)	1
Metabolism and nutrition disorders
Decreased appetite * 1	1/374 (0.27%)	1
Dehydration * 1	2/374 (0.53%)	3
Feeding intolerance * 1	1/374 (0.27%)	1
Hyperammonaemia * 1	1/374 (0.27%)	1
Hyponatraemia * 1	1/374 (0.27%)	2
Musculoskeletal and connective tissue disorders
Aneurysmal bone cyst * 1	1/374 (0.27%)	1
Foot deformity * 1	1/374 (0.27%)	1
Nervous system disorders
Cerebral haemorrhage * 1	1/374 (0.27%)	1
Change in seizure presentation * 1	5/374 (1.34%)	6
Dystonia * 1	1/374 (0.27%)	1
Encephalopathy * 1	1/374 (0.27%)	1
Epilepsy * 1	1/374 (0.27%)	1
Febrile convulsion * 1	2/374 (0.53%)	2
Generalised tonic-clonic seizure * 1	2/374 (0.53%)	4
Hyperkinesia * 1	2/374 (0.53%)	2
Hypotonia * 1	1/374 (0.27%)	1
Lethargy * 1	1/374 (0.27%)	1
Movement disorder * 1	2/374 (0.53%)	2
Myoclonus * 1	1/374 (0.27%)	1
Petit mal epilepsy * 1	1/374 (0.27%)	1
Seizure * 1	21/374 (5.61%)	26
Seizure cluster * 1	6/374 (1.60%)	9
Status epilepticus * 1	15/374 (4.01%)	18
Psychiatric disorders
Acute psychosis * 1	1/374 (0.27%)	4
Agitation * 1	1/374 (0.27%)	1
Apathy * 1	1/374 (0.27%)	1
Insomnia * 1	3/374 (0.80%)	3
Tic * 1	1/374 (0.27%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome * 1	1/374 (0.27%)	1
Acute respiratory failure * 1	2/374 (0.53%)	2
Apnoea * 1	1/374 (0.27%)	1
Respiratory distress * 1	2/374 (0.53%)	2
Skin and subcutaneous tissue disorders
Erythema multiforme * 1	1/374 (0.27%)	1
Urticaria * 1	1/374 (0.27%)	1
Surgical and medical procedures
Labial frenectomy * 1	1/374 (0.27%)	1
1 Term from vocabulary, MedDRA version 19.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Any ZX008 Open Label Dose
	Affected / at Risk (%)	# Events
Total	342/374 (91.44%)
Gastrointestinal disorders
Constipation * 1	23/374 (6.15%)	34
Diarrhoea * 1	73/374 (19.52%)	102
Vomiting * 1	39/374 (10.43%)	50
General disorders
Fatigue * 1	34/374 (9.09%)	49
Pyrexia * 1	112/374 (29.95%)	229
Infections and infestations
Ear infection * 1	39/374 (10.43%)	56
Gastroenteritis * 1	32/374 (8.56%)	34
Gastroenteritis viral * 1	20/374 (5.35%)	21
Influenza * 1	45/374 (12.03%)	50
Nasopharyngitis * 1	104/374 (27.81%)	224
Rhinitis * 1	32/374 (8.56%)	62
Upper respiratory tract infection * 1	65/374 (17.38%)	117
Viral infection * 1	27/374 (7.22%)	40
Viral upper respiratory tract infection * 1	19/374 (5.08%)	36
Injury, poisoning and procedural complications
Fall * 1	25/374 (6.68%)	26
Investigations
Blood glucose decreased * 1	88/374 (23.53%)	115
Echocardiogram abnormal * 1	67/374 (17.91%)	82
Weight decreased * 1	31/374 (8.29%)	33
Metabolism and nutrition disorders
Decreased appetite * 1	100/374 (26.74%)	112
Hypoglycaemia * 1	32/374 (8.56%)	35
Nervous system disorders
Seizure * 1	46/374 (12.30%)	60
Somnolence * 1	35/374 (9.36%)	38
Tremor * 1	21/374 (5.61%)	24
Psychiatric disorders
Abnormal behaviour * 1	22/374 (5.88%)	28
Irritability * 1	19/374 (5.08%)	23
Respiratory, thoracic and mediastinal disorders
Cough * 1	34/374 (9.09%)	55
Skin and subcutaneous tissue disorders
Rash * 1	20/374 (5.35%)	20
1 Term from vocabulary, MedDRA version 19.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB
• Organization: Cares
• Phone: 001 844 599 2273
• EMail: UCBCares@ucb.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cross JH, Galer BS, Gil-Nagel A, Devinsky O, Ceulemans B, Lagae L, Schoonjans AS, Donner E, Wirrell E, Kothare S, Agarwal A, Lock M, Gammaitoni AR. Impact of fenfluramine on the expected SUDEP mortality rates in patients with Dravet syndrome. Seizure. 2021 Dec;93:154-159. doi: 10.1016/j.seizure.2021.10.024. Epub 2021 Nov 2.

• Responsible Party: UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )
• ClinicalTrials.gov Identifier: NCT02823145
• Other Study ID Numbers: ZX008-1503; 2016-002804-14 ( EudraCT Number )
• First Submitted: June 13, 2016
• First Posted: July 6, 2016
• Results First Submitted: July 27, 2023
• Results First Posted: September 25, 2023
• Last Update Posted: September 25, 2023