A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) in Children and Young Adults With Dravet Syndrome

• ClinicalTrials.gov Identifier: NCT02682927
• Recruitment Status: Completed
• First Posted: February 17, 2016
• Results First Posted: October 19, 2022
• Last Update Posted: September 28, 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: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Dravet Syndrome; Seizure Disorder
• Interventions: Drug: ZX008 (Fenfluramine Hydrochloride); Drug: Matching Placebo
• Enrollment: 262

Participant Flow

Recruitment Details	The study 1501 started to enroll participants in January 2016 and concluded in July 2020. The study 1502 started to enroll participants in July 2016 and concluded in July 2020. The consolidated results of Study 1 and Study 3 are included in this record. The Participant Flow refers to the Randomized Population.
Pre-assignment Details	Due to slow enrollment into both trials, the databases for the two trials were combined. The first 72 enrolled participants from ZX008-1501 and first 47 from ZX008-1502 were combined for an analysis and reported as Study 1, whereas the final 55 participants from ZX008- 1501 and the final 88 from ZX008-1502 were combined and reported as Study 3.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Period Title: Overall Study
Started	40	39	40	48	46	49
Completed	37	39	34	43	45	46
Not Completed	3	0	6	5	1	3
Reason Not Completed
Adverse Event	0	0	5	1	0	2
Death	0	0	0	1	0	0
Lack of Efficacy	1	0	0	1	0	0
Other	0	0	0	2	0	0
Withdrawal by Subject	2	0	1	0	1	1

Baseline Characteristics

Arm/Group Title		Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day	Total
Arm/Group Description		Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Total of all reporting groups
Overall Number of Baseline Participants		40	39	40	48	46	49	262
Baseline Analysis Population Description		Baseline characteristics refers to the Randomized population which included all participants randomized to receive study treatment.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	40 participants	39 participants	40 participants	48 participants	46 participants	49 participants	262 participants
		9.2 (5.10)	9.0 (4.52)	8.8 (4.41)	9.0 (4.29)	9.6 (4.42)	9.5 (5.29)	9.2 (4.65)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	40 participants	39 participants	40 participants	48 participants	46 participants	49 participants	262 participants
24 Months - <12 Years		27 67.5%	28 71.8%	31 77.5%	31 64.6%	30 65.2%	30 61.2%	177 67.6%
12 - < 18 Years		10 25.0%	11 28.2%	7 17.5%	17 35.4%	15 32.6%	16 32.7%	76 29.0%
18 - < 65 Years		3 7.5%	0 0.0%	2 5.0%	0 0.0%	1 2.2%	3 6.1%	9 3.4%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	39 participants	40 participants	48 participants	46 participants	49 participants	262 participants
	Female	19 47.5%	17 43.6%	19 47.5%	21 43.8%	22 47.8%	27 55.1%	125 47.7%
	Male	21 52.5%	22 56.4%	21 52.5%	27 56.3%	24 52.2%	22 44.9%	137 52.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	40 participants	39 participants	40 participants	48 participants	46 participants	49 participants	262 participants
White		31 77.5%	33 84.6%	34 85.0%	36 75.0%	37 80.4%	34 69.4%	205 78.2%
Black or African American		0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.2%	1 2.0%	2 0.8%
Asian		4 10.0%	2 5.1%	1 2.5%	7 14.6%	5 10.9%	8 16.3%	27 10.3%
American Indian or Alaska Native		1 2.5%	1 2.6%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 0.8%
Other		2 5.0%	1 2.6%	1 2.5%	4 8.3%	2 4.3%	3 6.1%	13 5.0%
Not Reported		2 5.0%	2 5.1%	4 10.0%	1 2.1%	0 0.0%	1 2.0%	10 3.8%
Unknown		0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.2%	2 4.1%	3 1.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Mean Convulsive Seizures Frequency (MCSF) to the Combined Titration and Maintenance Periods (T+M) in Participants Receiving ZX008 0.8 mg/kg/Day Compared to Placebo
Description	Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	40	48	48
Mean (Standard Deviation); Unit of Measure: seizure frequency per 28 days
	-6.71 (24.263)	-13.11 (25.500)	1.54 (21.966)	-3.54 (124.132)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study 1: Placebo, Study 1: ZX008 0.8 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage difference from Placebo
	Estimated Value	62.29
	Confidence Interval	(2-Sided) 95%; 47.72 to 72.80
	Estimation Comments	Estimate was obtained from the LSMeans on the log scale as follows: 100 x [1 - exp(LS mean active - LS mean placebo).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study 3: Placebo, Study 3: ZX008 0.8 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage difference from Placebo
	Estimated Value	64.75
	Confidence Interval	(2-Sided) 95%; 51.85 to 74.19
	Estimation Comments	Estimate was obtained from the LSMeans on the log scale as follows: 100 x [1 - exp(LS mean active - LS mean placebo).

2. Secondary Outcome

Title	Change From Baseline in the Mean Convulsive Seizures Frequency to the Combined Titration and Maintenance Period (T+M) in Participants Receiving ZX008 0.2 mg/kg/Day Compared to Placebo
Description	Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	48	46
Mean (Standard Deviation); Unit of Measure: seizure frequency per 28 days
	-6.71 (24.263)	-18.81 (90.640)	1.54 (21.966)	-5.89 (84.735)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study 1: Placebo, Study 1: ZX008 0.2 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage difference from Placebo
	Estimated Value	32.43
	Confidence Interval	(2-Sided) 95%; 6.19 to 51.33
	Estimation Comments	Estimate was obtained from the LSMeans on the log scale as follows: 100 x [1 - exp(LS mean active - LS mean placebo).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study 3: Placebo, Study 3: ZX008 0.2 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage difference from Placebo
	Estimated Value	49.88
	Confidence Interval	(2-Sided) 95%; 31.31 to 63.43
	Estimation Comments	Estimate was obtained from the LSMeans on the log scale as follows: 100 x [1 - exp(LS mean active - LS mean placebo).

3. Secondary Outcome

Title	Percentage of Participants Who Achieved Greater Than or Equal to 25% (≥25%) Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period
Description	Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 25% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
	35.0	66.7	90.0	27.1	71.7	83.3

4. Secondary Outcome

Title	Percentage of Participants Who Achieved a ≥50% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period
Description	Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 50% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
	12.5	38.5	67.5	6.3	45.7	72.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study 1: Placebo, Study 1: ZX008 0.2 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.773
	Confidence Interval	(2-Sided) 95%; 1.475 to 15.450
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study 1: Placebo, Study 1: ZX008 0.8 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	14.960
	Confidence Interval	(2-Sided) 95%; 4.484 to 49.915
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Study 3: Placebo, Study 3: ZX008 0.2 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	13.4
	Confidence Interval	(2-Sided) 95%; 3.6 to 49.8
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Study 3: Placebo, Study 3: ZX008 0.8 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	53.3
	Confidence Interval	(2-Sided) 95%; 12.9 to 220.5
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Percentage of Participants Who Achieved a ≥75% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period
Description	Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 75% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
	2.5	23.1	50.0	4.2	28.3	47.9

6. Secondary Outcome

Title	Percentage of Participants Who Achieved a 100% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period
Description	Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 100% reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
	0	7.7	7.5	0	0	12.5

7. Secondary Outcome

Title	Longest Convulsive Seizure-free Interval in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period
Description	The longest interval between convulsive seizures was calculated over the entire Titration and Maintenance Period and was derived as the maximum of the number of days between consecutive convulsive seizures.
Time Frame	During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Median (Full Range); Unit of Measure: days
	9.50; (2.0 to 23.0)	15.00; (3.0 to 106.0)	25.00; (2.0 to 97.0)	10; (2 to 65)	18.5; (2 to 100)	30; (2 to 104)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study 1: Placebo, Study 1: ZX008 0.2 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.035
	Comments	[Not Specified]
	Method	Wilcoxon rank sum test
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study 1: Placebo, Study 1: ZX008 0.8 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Wilcoxon rank sum test
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Study 3: Placebo, Study 3: ZX008 0.2 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0002
	Comments	[Not Specified]
	Method	Wilcoxon rank sum test
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Study 3: Placebo, Study 3: ZX008 0.8 mg/kg/Day
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Wilcoxon rank sum test
	Comments	[Not Specified]

8. Secondary Outcome

Title	Number of Convulsive Seizure-free Days in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period
Description	A convulsive seizure free day was defined as a day for which diary data are available and no convulsive seizures were reported. Convulsive seizure free days were taken from the electronic diary data.
Time Frame	During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Median (Full Range); Unit of Measure: seizure free days
	15.14; (1.1 to 25.6)	20.86; (2.2 to 28.0)	24.43; (1.0 to 28.0)	20.20; (1.4 to 27.1)	23.36; (0.8 to 27.7)	25.33; (0.3 to 28.0)

9. Secondary Outcome

Title	Change From Baseline in Non-convulsive Seizure Frequency to the Combined Titration and Maintenance Period in Each ZX008 Treatment Arm Compared to Placebo
Description	Non-convulsive seizures included focal without clear observable motor signs, absence or atypical absence, myoclonic and atonic. The number of non-convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day non-convulsive seizure frequency.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	21	23	24	26	25	30
Median (Full Range); Unit of Measure: seizure frequency per 28 days
	-9.38; (-198.8 to 1886.1)	-4.85; (-1940.8 to 192.3)	-20.06; (-2064.8 to 9.4)	-0.68; (-160.0 to 1313.1)	-0.67; (-138.7 to 111.3)	-4.35; (-1410.6 to 107.5)

10. Secondary Outcome

Title	Change From Baseline in Convulsive + Non-convulsive Seizure Frequency to the Combined Titration and Maintenance Period in Each ZX008 Treatment Arm Compared to Placebo
Description	Total seizure frequency were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). Non-convulsive seizures included focal without clear observable motor signs, absence or atypical absence, myoclonic and atonic. The seizure frequency was based on electronic diary data obtained for each participant. The number of all seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day convulsive or non-convulsive seizure frequency.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Median (Full Range); Unit of Measure: seizure frequency per 28 days
	-4.45; (-198.4 to 1850.1)	-7.40; (-1955.1 to 187.1)	-22.95; (-2069.3 to 44.5)	-1.09; (-160.1 to 1310.5)	-6.54; (-153.0 to 525.9)	-11.39; (-1504.8 to 791.4)

11. Secondary Outcome

Title	Percentage of Participants With Rescue Medication Usage in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period
Description	Rescue medication was administered according to each participant's usual or prescribed regimen consisting of 1 or more medications. The usage of rescue medication (number of days and number of medications used per seizure episode) was based on electronic diary data obtained for each participant. The number of days rescue medication was taken (normalized to 28 days) was calculated for each participant. Multiple medications taken on the same day were counted once for that day.
Time Frame	From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
	77.5	59.0	45.0	60.4	65.2	47.9

12. Secondary Outcome

Title	Percentage of Participants With Hospitalization and Healthcare Resource Utilization to Treat Seizures in Each ZX008 Treatment Arm Compared to Placebo During Study
Description	Participants who utilized medical center care to treat a seizure during the study were reported.
Time Frame	During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
	22.5	17.9	15.0	12.5	19.6	14.6

13. Secondary Outcome

Title	Percentage of Participants With Status Epilepticus (SE) in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period
Description	The participants who either had SE episode recorded as an adverse event (AE) during treatment or a seizure greater than 10 minutes were reported for each treatment group. Additionally, a single participant who may had more than one episode of SE, and an episode of SE recorded as both an AE and as a seizure longer than 10 minutes was counted as a single event.
Time Frame	During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
	27.5	28.2	35.0	16.7	19.6	25.0

14. Secondary Outcome

Title	Distribution of Duration of Convulsive Seizures (in Percentage) in Each ZX008 Treatment Arm Compared to Placebo at Baseline and During the Titration and Maintenance Period
Description	Duration of single convulsive seizures during the Baseline and the duration over the Titration and Maintenance Period were reported by treatment group using categories as <2 minutes, 2 to 10 minutes and > 10 minutes as collected in the seizure diary.
Time Frame	At Baseline and 14 weeks of Titration (2 weeks) and Maintenance Period (12 weeks)

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of seizures
<2 min (Baseline)	69.28	64.13	71.61	64.21	63.90	74.11
2-10 min (Baseline)	26.86	34.95	24.22	34.83	33.66	22.78
>10 min (Baseline)	3.86	0.93	4.17	0.96	2.45	3.10
<2 min (Titration + Maintenance Period)	71.31	71.59	72.27	65.84	63.45	84.67
2-10 min (Titration + Maintenance Period)	26.31	25.61	22.91	33.74	31.34	13.71
>10 min (Titration + Maintenance Period)	2.38	2.79	4.82	0.43	5.22	1.62

15. Secondary Outcome

Title	Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Rating Score, as Assessed by the Principal Investigator in Each ZX008 Treatment Arm Compared to Placebo
Description	CGI-I scale measures improvement in the participant's clinical status 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. The Principal Investigator rated their global impression of the participant's condition during the study.
Time Frame	At Visit 6 (Day 15), 8 (Day 43), 10 (Day 71) and 12 (Day 99)

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
1 = Very much improved (Visit 6)	5.0	23.1	17.5	4.2	21.7	16.7
2 = Much improved (Visit 6)	12.5	12.8	25.0	2.1	21.7	27.1
3 = Minimally improved (Visit 6)	20.0	20.5	20.0	27.1	17.4	27.1
4 = No change (Visit 6)	40.0	25.6	17.5	54.2	26.1	12.5
5 = Minimally worse (Visit 6)	5.0	7.7	5.0	4.2	2.2	2.1
6 = Much worse (Visit 6)	0	0	2.5	0	0	4.2
7 = Very much worse (Visit 6)	0	0	0	0	0	0
1 = Very much improved (Visit 8)	0	5.1	17.5	4.2	17.4	29.2
2 = Much improved (Visit 8)	12.5	30.8	37.5	6.3	10.9	31.3
3 = Minimally improved (Visit 8)	30.0	20.5	10.0	16.7	26.1	14.6
4 = No change (Visit 8)	30.0	17.9	10.0	50.0	34.8	8.3
5 = Minimally worse (Visit 8)	5.0	5.1	0	4.2	0	4.2
6 = Much worse (Visit 8)	2.5	5.1	2.5	2.1	0	0
7 = Very much worse (Visit 8)	0	0	2.5	0	0	0
1 = Very much improved (Visit 10)	2.5	17.9	20.0	4.2	15.2	35.4
2 = Much improved (Visit 10)	7.5	17.9	47.5	10.4	19.6	18.8
3 = Minimally improved (Visit 10)	30.0	25.6	5.0	12.5	26.1	16.7
4 = No change (Visit 10)	35.0	28.2	7.5	60.4	28.3	4.2
5 = Minimally worse (Visit 10)	10.0	7.7	0	0	0	0
6 = Much worse (Visit 10)	0	2.6	0	0	0	2.1
7 = Very much worse (Visit 10)	0	0	0	0	0	0
1 = Very much improved (Visit 12)	2.5	12.8	27.5	4.2	8.7	33.3
2 = Much improved (Visit 12)	7.5	28.2	35.0	4.2	28.3	31.3
3 = Minimally improved (Visit 12)	30.0	17.9	15.0	16.7	21.7	10.4
4 = No change (Visit 12)	47.5	28.2	12.5	58.3	28.3	16.7
5 = Minimally worse (Visit 12)	2.5	10.3	0	6.3	10.9	6.3
6 = Much worse (Visit 12)	2.5	2.6	0	0	0	0
7 = Very much worse (Visit 12)	0	0	2.5	0	0	0

16. Secondary Outcome

Title	Percentage of Participants With Clinical Global Impression - Improvement Rating Score, as Assessed by the Parent/Caregiver in Each ZX008 Treatment Arm Compared to Placebo
Description	CGI-I scale measures improvement in the participant's clinical status 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. The Parent/Caregiver rated their global impression of the participant's condition during the study.
Time Frame	At Visit 6 (Day 15), 8 (Day 43), 10 (Day 71) and 12 (Day 99)

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Measure Type: Number; Unit of Measure: percentage of participants
1 = Very much improved (Visit 6)	2.5	17.9	15.0	6.3	13.0	16.7
2 = Much improved (Visit 6)	22.5	20.5	27.5	2.1	23.9	31.3
3 = Minimally improved (Visit 6)	12.5	28.2	22.5	25.0	26.1	31.3
4 = No change (Visit 6)	45.0	12.8	20.0	45.8	19.6	2.1
5 = Minimally worse (Visit 6)	2.5	7.7	2.5	10.4	2.2	6.3
6 = Much worse (Visit 6)	5.0	2.6	7.5	2.1	2.2	2.1
7 = Very much worse (Visit 6)	0	0	2.5	0	0	2.1
1 = Very much improved (Visit 8)	0	15.4	20.0	4.2	6.5	39.6
2 = Much improved (Visit 8)	15.0	25.6	37.5	8.3	30.4	29.2
3 = Minimally improved (Visit 8)	25.0	25.6	15.0	20.8	28.3	14.6
4 = No change (Visit 8)	20.0	12.8	5.0	47.9	17.4	6.3
5 = Minimally worse (Visit 8)	15.0	10.3	2.5	6.3	6.5	0
6 = Much worse (Visit 8)	2.5	5.1	5.0	4.2	2.2	2.1
7 = Very much worse (Visit 8)	0	0	2.5	4.2	0	0
1 = Very much improved (Visit 10)	2.5	20.5	35.0	2.1	8.7	41.7
2 = Much improved (Visit 10)	12.5	17.9	30.0	6.3	28.3	22.9
3 = Minimally improved (Visit 10)	22.5	20.5	7.5	25.0	26.1	8.3
4 = No change (Visit 10)	32.5	25.6	10.0	45.8	26.1	6.3
5 = Minimally worse (Visit 10)	12.5	7.7	0	6.3	0	4.2
6 = Much worse (Visit 10)	2.5	7.7	0	0	4.3	0
7 = Very much worse (Visit 10)	2.5	0	2.5	0	0	0
1 = Very much improved (Visit 12)	2.5	20.5	27.5	2.1	6.5	33.3
2 = Much improved (Visit 12)	7.5	20.5	27.5	6.3	28.3	29.2
3 = Minimally improved (Visit 12)	20.0	15.4	10.0	18.8	30.4	20.8
4 = No change (Visit 12)	35.0	20.5	15.0	50.0	13.0	4.2
5 = Minimally worse (Visit 12)	17.5	15.4	5.0	10.4	8.7	4.2
6 = Much worse (Visit 12)	7.5	7.7	5.0	2.1	4.3	2.1
7 = Very much worse (Visit 12)	0	0	2.5	0	2.2	2.1

17. Secondary Outcome

Title	Change From Baseline to Day 99 in the Quality of Life in Childhood Epilepsy (QOLCE) Score to Measure Quality of Life in Each ZX008 Treatment Arm Compared to Placebo
Description	QOLCE is a low-burden parent/caregiver completed assessment that evaluates how epilepsy affects day-to day functioning of the participant in various life areas, including physical activities, well being, cognition, social activities, behavior, and general health. QOLCE scores items on 16 subscales with possible 5-point response for each, where scores of 5 was best possible response and 1 was worst possible response. Item scores were then transformed to a 0-100 scale as follows: 1-0, 2-25, 3-50, 4-75, 5-100. A score for each participant for each subscale was calculated by averaging that participant's responses to each item in the subscale. Subscale scores per participant were averaged to obtain an overall QoL score for each participant. Higher the subscale and overall QoL scores, better the response.
Time Frame	From Baseline to Day 99

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Mean (Standard Deviation); Unit of Measure: score on a scale
	1.5 (8.73)	0.8 (11.77)	5.8 (11.70)	1.2 (9.01)	6.1 (12.47)	5.5 (13.22)

18. Secondary Outcome

Title	Change From Baseline to Day 99 in the Overall Quality of Life Score From the Pediatric Quality of Life Inventory™ (PedsQL) Score in Each ZX008 Treatment Arm Compared to Placebo
Description	The Pediatric Quality of Life Inventory (PedsQL) is a pediatric modular measure of health related quality of life (QoL) completed by the parent/caregiver on behalf of the participant. It consisted of 23 items across 4 core scales that measure physical (8 items), emotional, social, and school functioning (5 items each). Each of the responses to the 23 items is initially scored on a 5-point Likert scale from 0 (Never) to 4 (Almost always). Scores are linearly transformed to a scale of 0 to 100, where 0=100, 1=75, 2=50, 3=25 and 4=0, and higher scores correspond to better health-related QoL. The Overall Quality of Life is the average of all the items over the number of items answered on all the Scales.
Time Frame	From Baseline to Day 99

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	48	46	48
Mean (Standard Deviation); Unit of Measure: score on a scale
	-1.6 (10.43)	6.8 (11.25)	5.9 (15.11)	1.9 (13.26)	4.2 (17.65)	2.1 (14.73)

19. Secondary Outcome

Title	Change From Baseline to Day 99 in the Total Score From PedsQL Family Impact Module Score in Each ZX008 Treatment Arm Compared to Placebo
Description	The PedsQL Family Impact measured the impact of pediatric chronic health conditions on parents and the family by measuring parent self-reported physical, emotional, social, and cognitive functioning, communication, worry, and family daily activities and relationships. There are a total of 36 items in the PedsQL: 6 items for Physical Functioning, 5 items each for Emotional Functioning, Cognitive Functioning and Worry, 4 for Social Functioning, 3 for Communication, 3 questions for Daily Activities, and 5 for Family Relationships. Each of the responses are initially scored on a 5-point Likert scale from 0 (Never) to 4 (Almost always) and then linearly transformed to a scale of 0 to 100, where 0=100, 1=75, 2=50, 3=25 and 4=0, and higher scores mean better health-related QoL.
Time Frame	From Baseline to Day 99

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	40	39	40	47	44	48
Mean (Standard Deviation); Unit of Measure: score on a scale
	-4.4 (13.00)	3.9 (9.44)	5.4 (15.60)	1.3 (14.88)	0.7 (15.78)	6.3 (14.64)

20. Secondary Outcome

Title	Quality of Life (QoL) of the Parent/Caregiver Using the EQ- 5D-5L Scale in Each ZX008 Treatment Arm Compared to Placebo at Baseline and Day 99
Description	The EuroQOL-5 Dimensions-5 Levels scale produced by European QOL Group (EQ-5D-5L) health questionnaire is a health-related QOL instrument with 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The 5 dimensions of EQ-5D-5L health questionnaire were assessed on a Likert scale with 5 possible levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The categories "slight problems", "moderate problems", "severe problems" and "extreme problems" are collapsed into one response category "problems. The QOL of the parent/caregiver was assessed and percentage of participants was reported for each item.
Time Frame	At Baseline and Day 99

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.

Arm/Group Title		Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:		Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed		39	37	39	42	43	45
Measure Type: Number; Unit of Measure: percentage of participants
Mobility- No problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		33.33	52.94	46.15	40.00	54.55	28.57
Mobility- Problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		66.67	47.06	53.85	60.00	45.45	71.43
Mobility- No problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		40.00	45.95	51.35	52.38	51.16	46.67
Mobility- Problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		60.00	54.05	48.65	47.62	48.84	53.33
Self-care - No problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		25.64	41.18	38.46	22.50	36.36	22.86
Self-care - Problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		74.36	58.82	61.54	77.50	63.64	77.14
Self-care - No problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		28.57	43.24	48.65	30.95	34.88	35.56
Self-care - Problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		71.43	56.76	51.35	69.05	65.12	64.44
Usual activities- No problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		23.08	41.18	35.90	25.00	39.39	20.00
Usual activities- Problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		76.92	58.82	64.10	75.00	60.61	80.00
Usual activities- No problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		25.71	32.43	48.65	30.95	25.58	35.56
Usual activities- Problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		74.29	67.57	51.35	69.05	74.42	64.44
Pain/discomfort- No problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		48.72	41.18	46.15	45.00	51.52	51.43
Pain/discomfort- Problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		51.28	58.82	53.85	55.00	48.48	48.57
Pain/discomfort- No problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		48.57	51.35	64.86	76.19	46.51	64.44
Pain/discomfort- Problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		51.43	48.65	35.14	45.24	53.49	35.56
Anxiety/depression- No problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		74.36	61.76	56.41	60.00	63.64	74.29
Anxiety/depression- Problems (Baseline)	Number Analyzed	39 participants	34 participants	39 participants	40 participants	33 participants	35 participants
		25.64	38.24	43.59	40.00	36.36	25.71
Anxiety/depression- No problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		65.71	67.57	67.57	69.05	67.44	73.33
Anxiety/depression- Problems (Day 99)	Number Analyzed	35 participants	37 participants	37 participants	42 participants	43 participants	45 participants
		34.29	32.43	32.43	30.95	32.56	26.67

21. Secondary Outcome

Title	Change From Baseline to Day 99 in Affective Symptoms of the Parent/Caregiver Using the Hospital Anxiety and Depression Scale (HADS) in Each ZX008 Treatment Arm Compared to Placebo
Description	The HADS is a tool that was validated to assess presence of anxiety or depression in an outpatient non-psychiatric population. The HADS a 14-item scale that generates ordinal data for 2 dimensions: 1) Anxiety (7 items), and 2) Depression (7 items). Each item has 4 possible answers rated 0 to 3, of which 0 = No distress and 3 = worst distress. All answers to the items for a dimension with their respective rating are added resulting in a range for each dimension from 0-21, out of which of 0-7 = normal; 8-10=borderline abnormal; 11-21=abnormal. Scores for the entire scale (emotional distress) range from 0 to 42, with higher scores indicating more distress.
Time Frame	From Baseline to Day 99

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Study 1: Placebo	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: Placebo	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	31	32	35	30	31	27
Mean (Standard Deviation); Unit of Measure: score on a scale
Anxiety	-0.4 (2.68)	-0.8 (2.84)	-0.8 (3.33)	-0.6 (3.62)	0.2 (3.89)	-0.7 (4.00)
Depression	0.8 (4.50)	0.2 (4.52)	0.1 (4.35)	-0.7 (3.80)	2.0 (4.77)	-0.8 (4.03)
Total emotional distress	0.4 (6.45)	-0.6 (6.60)	-0.7 (6.82)	-1.2 (6.42)	2.2 (7.52)	-1.5 (6.61)

22. Secondary Outcome

Title	Maximum Observed Concentration of ZX008 Determined Directly From the Concentration Time Profile [Cmax] at Steady State
Description	Cmax is the maximum observed concentration determined directly from the concentration-time profile.
Time Frame	At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose

Outcome Measure Data

Analysis Population Description

PK population for each study represents participants randomized to ZX008 and provided concentrations for use in the population PK analysis.

Arm/Group Title	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	39	36	45	44
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms per milliliter (ng/mL)
	17.7; (32.5%)	67.9; (37.4%)	17.4; (32.3%)	64.5; (36.6%)

23. Secondary Outcome

Title	Area Under the Concentration Time Curve of ZX008 From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State
Description	AUC0-24 is the area under the concentration time curve from time zero to 24 hours.
Time Frame	At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose

Outcome Measure Data

Analysis Population Description

PK population for each study represents participants randomized to ZX008 and provided concentrations for use in the population PK analysis. PK samples at Visit 8 (Day 43) taken pre-dose to 6 hours post-dose were used to develop a population PK model. The model was utilized to generate plasma concentration-time curve over 24 hours at steady-state in study participants. AUC0-24 was calculated by numerical integration of the individual predicted concentration-time curve.

Arm/Group Title	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	39	36	45	44
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram*hour per milliliter (ng*h/mL)
	356; (37.0%)	1390; (41.3%)	348; (37.1%)	1290; (42.6%)

24. Secondary Outcome

Title	Time to Maximum Concentration [Tmax] of ZX008 at Steady State
Description	Tmax is the time to maximum concentration at steady state.
Time Frame	At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose

Outcome Measure Data

Analysis Population Description

PK population for each study represents participants randomized to ZX008 and provided concentrations for use in the population PK analysis.

Arm/Group Title	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	39	36	45	44
Median (Full Range); Unit of Measure: hours (h)
	2.90; (2.80 to 3.10)	3.00; (2.70 to 3.20)	2.90; (2.80 to 3.10)	2.90; (2.70 to 3.20)

25. Secondary Outcome

Title	Elimination Half-life [t1/2 Beta] of ZX008 at Steady State
Description	t1/2 beta is the elimination half-life.
Time Frame	At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose

Outcome Measure Data

Analysis Population Description

PK population for each study represents participants randomized to ZX008 and provided concentrations for use in the population PK analysis.

Arm/Group Title	Study 1: ZX008 0.2 mg/kg/Day	Study 1: ZX008 0.8 mg/kg/Day	Study 3: ZX008 0.2 mg/kg/Day	Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description:	Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.	Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
Overall Number of Participants Analyzed	39	36	45	44
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours (h)
	18.4; (32.3%)	21.1; (51.8%)	18.1; (32.1%)	18.6; (42.2%)

Adverse Events

Time Frame	From Titration Period until the Safety Follow-up Visit (up to Day 113)
Adverse Event Reporting Description	A Treatment emergent adverse event (TEAE) was defined as any AE that based on start date information occurred after the first dose of study drug. The safety population included all randomized participants who received at least 1 dose of ZX008 or placebo.
Arm/Group Title	Study 1: Placebo		Study 1: ZX008 0.2 mg/kg/Day		Study 1: ZX008 0.8 mg/kg/Day		Study 3: Placebo		Study 3: ZX008 0.2 mg/kg/Day		Study 3: ZX008 0.8 mg/kg/Day
Arm/Group Description	Participants received matching placebo as an oral solution, twice a day (bid) in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.		Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.		Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 1 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.		Participants received matching placebo as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.		Participants received ZX008 0.2 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.		Participants received ZX008 0.8 mg/kg/day as an oral solution, bid, in equally divided doses with food for up to approximately 16 weeks. Study 3 is the merged analysis of 2 identical (ZX008-1501 and ZX008-1502) studies.
All-Cause Mortality
	Study 1: Placebo		Study 1: ZX008 0.2 mg/kg/Day		Study 1: ZX008 0.8 mg/kg/Day		Study 3: Placebo		Study 3: ZX008 0.2 mg/kg/Day		Study 3: ZX008 0.8 mg/kg/Day
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/40 (0.00%)		0/39 (0.00%)		0/40 (0.00%)		1/48 (2.08%)		0/46 (0.00%)		0/48 (0.00%)
Serious Adverse Events
	Study 1: Placebo		Study 1: ZX008 0.2 mg/kg/Day		Study 1: ZX008 0.8 mg/kg/Day		Study 3: Placebo		Study 3: ZX008 0.2 mg/kg/Day		Study 3: ZX008 0.8 mg/kg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/40 (10.00%)		4/39 (10.26%)		5/40 (12.50%)		2/48 (4.17%)		3/46 (6.52%)		3/48 (6.25%)
Gastrointestinal disorders
Diarrhoea * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
General disorders
Adverse drug reaction * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Sudden unexplained death in epilepsy * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	1/48 (2.08%)	1	0/46 (0.00%)	0	0/48 (0.00%)	0
Infections and infestations
Gastroenteritis * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	1/46 (2.17%)	1	0/48 (0.00%)	0
Gastroenteritis viral * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	1/48 (2.08%)	1	0/46 (0.00%)	0	0/48 (0.00%)	0
Lower respiratory tract infection * 1	0/40 (0.00%)	0	1/39 (2.56%)	2	0/40 (0.00%)	0	1/48 (2.08%)	1	0/46 (0.00%)	0	0/48 (0.00%)	0
Pneumonia * 1	1/40 (2.50%)	1	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Varicella * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	1/48 (2.08%)	1
Injury, poisoning and procedural complications
Head injury * 1	1/40 (2.50%)	1	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Skull fracture * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	1/46 (2.17%)	1	0/48 (0.00%)	0
Toxicity to various agents * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	1/48 (2.08%)	1
Investigations
Hepatic enzyme increased * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	1/48 (2.08%)	1
Weight decreased * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Nervous system disorders
Febrile convulsion * 1	1/40 (2.50%)	1	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Generalised tonic-clonic seizure * 1	1/40 (2.50%)	1	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Lethargy * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Seizure * 1	1/40 (2.50%)	1	1/39 (2.56%)	1	1/40 (2.50%)	1	1/48 (2.08%)	2	1/46 (2.17%)	1	0/48 (0.00%)	0
Somnolence * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Status epilepticus * 1	2/40 (5.00%)	2	1/39 (2.56%)	1	2/40 (5.00%)	3	0/48 (0.00%)	0	1/46 (2.17%)	1	0/48 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia * 1	0/40 (0.00%)	0	1/39 (2.56%)	1	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Respiratory distress * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	1/46 (2.17%)	1	0/48 (0.00%)	0
1 Term from vocabulary, MedDRA v 19.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Study 1: Placebo		Study 1: ZX008 0.2 mg/kg/Day		Study 1: ZX008 0.8 mg/kg/Day		Study 3: Placebo		Study 3: ZX008 0.2 mg/kg/Day		Study 3: ZX008 0.8 mg/kg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/40 (55.00%)		35/39 (89.74%)		36/40 (90.00%)		37/48 (77.08%)		41/46 (89.13%)		41/48 (85.42%)
Gastrointestinal disorders
Diarrhoea * 1	3/40 (7.50%)	3	12/39 (30.77%)	14	7/40 (17.50%)	7	4/48 (8.33%)	4	7/46 (15.22%)	8	7/48 (14.58%)	7
Vomiting * 1	4/40 (10.00%)	5	4/39 (10.26%)	5	3/40 (7.50%)	3	3/48 (6.25%)	4	0/46 (0.00%)	0	3/48 (6.25%)	3
Constipation * 1	0/40 (0.00%)	0	1/39 (2.56%)	1	4/40 (10.00%)	4	0/48 (0.00%)	0	2/46 (4.35%)	2	1/48 (2.08%)	1
Salivary hypersecretion * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	1/40 (2.50%)	1	0/48 (0.00%)	0	1/46 (2.17%)	1	0/48 (0.00%)	0
General disorders
Fatigue * 1	1/40 (2.50%)	1	4/39 (10.26%)	4	4/40 (10.00%)	4	1/48 (2.08%)	1	3/46 (6.52%)	3	5/48 (10.42%)	5
Pyrexia * 1	8/40 (20.00%)	12	7/39 (17.95%)	12	2/40 (5.00%)	3	4/48 (8.33%)	5	5/46 (10.87%)	7	9/48 (18.75%)	11
Asthenia * 1	0/40 (0.00%)	0	1/39 (2.56%)	1	0/40 (0.00%)	0	1/48 (2.08%)	1	2/46 (4.35%)	2	3/48 (6.25%)	3
Gait disturbance * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	3/46 (6.52%)	3	1/48 (2.08%)	1
Infections and infestations
Nasopharyngitis * 1	5/40 (12.50%)	6	4/39 (10.26%)	4	7/40 (17.50%)	8	5/48 (10.42%)	8	4/46 (8.70%)	7	1/48 (2.08%)	1
Upper respiratory tract infection * 1	5/40 (12.50%)	7	8/39 (20.51%)	13	0/40 (0.00%)	0	2/48 (4.17%)	3	3/46 (6.52%)	4	4/48 (8.33%)	5
Croup infectious * 1	0/40 (0.00%)	0	3/39 (7.69%)	3	1/40 (2.50%)	1	0/48 (0.00%)	0	1/46 (2.17%)	1	0/48 (0.00%)	0
Ear infection * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	1/40 (2.50%)	1	2/48 (4.17%)	2	3/46 (6.52%)	3	0/48 (0.00%)	0
Influenza * 1	4/40 (10.00%)	4	0/39 (0.00%)	0	0/40 (0.00%)	0	2/48 (4.17%)	2	1/46 (2.17%)	3	1/48 (2.08%)	1
Rhinitis * 1	1/40 (2.50%)	1	3/39 (7.69%)	3	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	2/48 (4.17%)	2
Sinusitis * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	1/40 (2.50%)	1	1/48 (2.08%)	1	3/46 (6.52%)	4	1/48 (2.08%)	1
Urinary tract infection * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	0/40 (0.00%)	0	0/48 (0.00%)	0	2/46 (4.35%)	3	1/48 (2.08%)	3
Viral infection * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	0/48 (0.00%)	0	3/46 (6.52%)	3	2/48 (4.17%)	3
Injury, poisoning and procedural complications
Fall * 1	2/40 (5.00%)	2	4/39 (10.26%)	5	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	1/48 (2.08%)	1
Investigations
Blood glucose decreased * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	6/48 (12.50%)	7	11/46 (23.91%)	13	8/48 (16.67%)	8
Blood pressure diastolic increased * 1	1/40 (2.50%)	2	3/39 (7.69%)	3	3/40 (7.50%)	3	3/48 (6.25%)	3	3/46 (6.52%)	3	1/48 (2.08%)	1
Echocardiogram abnormal * 1	5/40 (12.50%)	5	7/39 (17.95%)	7	9/40 (22.50%)	13	5/48 (10.42%)	5	11/46 (23.91%)	11	8/48 (16.67%)	8
Blood pressure increased * 1	0/40 (0.00%)	0	3/39 (7.69%)	4	2/40 (5.00%)	2	4/48 (8.33%)	4	2/46 (4.35%)	2	2/48 (4.17%)	2
Blood pressure systolic increased * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	0/40 (0.00%)	0	1/48 (2.08%)	1	0/46 (0.00%)	0	0/48 (0.00%)	0
Blood prolactin increased * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	3/40 (7.50%)	3	0/48 (0.00%)	0	1/46 (2.17%)	1	0/48 (0.00%)	0
Heart rate increased * 1	1/40 (2.50%)	1	3/39 (7.69%)	3	1/40 (2.50%)	1	3/48 (6.25%)	4	1/46 (2.17%)	1	0/48 (0.00%)	0
Platelet count decreased * 1	0/40 (0.00%)	0	1/39 (2.56%)	1	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	4/48 (8.33%)	4
Weight decreased * 1	0/40 (0.00%)	0	5/39 (12.82%)	5	1/40 (2.50%)	1	0/48 (0.00%)	0	1/46 (2.17%)	1	4/48 (8.33%)	4
Metabolism and nutrition disorders
Decreased appetite * 1	2/40 (5.00%)	2	8/39 (20.51%)	11	14/40 (35.00%)	15	3/48 (6.25%)	3	12/46 (26.09%)	12	18/48 (37.50%)	22
Hypoglycaemia * 1	0/40 (0.00%)	0	1/39 (2.56%)	1	1/40 (2.50%)	1	1/48 (2.08%)	1	0/46 (0.00%)	0	3/48 (6.25%)	3
Nervous system disorders
Lethargy * 1	2/40 (5.00%)	2	4/39 (10.26%)	6	7/40 (17.50%)	8	2/48 (4.17%)	2	1/46 (2.17%)	1	3/48 (6.25%)	4
Somnolence * 1	3/40 (7.50%)	4	6/39 (15.38%)	6	3/40 (7.50%)	3	5/48 (10.42%)	5	5/46 (10.87%)	6	10/48 (20.83%)	10
Ataxia * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	3/40 (7.50%)	3	1/48 (2.08%)	1	0/46 (0.00%)	0	2/48 (4.17%)	2
Balance disorder * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	1/40 (2.50%)	1	1/48 (2.08%)	1	0/46 (0.00%)	0	2/48 (4.17%)	2
Drooling * 1	0/40 (0.00%)	0	3/39 (7.69%)	3	2/40 (5.00%)	2	0/48 (0.00%)	0	1/46 (2.17%)	1	2/48 (4.17%)	2
Headache * 1	1/40 (2.50%)	1	3/39 (7.69%)	5	0/40 (0.00%)	0	1/48 (2.08%)	1	1/46 (2.17%)	1	0/48 (0.00%)	0
Hypotonia * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	3/40 (7.50%)	3	0/48 (0.00%)	0	0/46 (0.00%)	0	1/48 (2.08%)	1
Sedation * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	0/40 (0.00%)	0	3/48 (6.25%)	3	0/46 (0.00%)	0	0/48 (0.00%)	0
Seizure * 1	4/40 (10.00%)	4	3/39 (7.69%)	5	2/40 (5.00%)	4	1/48 (2.08%)	1	0/46 (0.00%)	0	1/48 (2.08%)	1
Seizure cluster * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	0/40 (0.00%)	0	0/48 (0.00%)	0	1/46 (2.17%)	1	0/48 (0.00%)	0
Status epilepticus * 1	0/40 (0.00%)	0	1/39 (2.56%)	1	0/40 (0.00%)	0	0/48 (0.00%)	0	3/46 (6.52%)	5	0/48 (0.00%)	0
Tremor * 1	1/40 (2.50%)	1	1/39 (2.56%)	1	1/40 (2.50%)	1	1/48 (2.08%)	1	1/46 (2.17%)	1	6/48 (12.50%)	6
Psychiatric disorders
Abnormal behaviour * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	3/40 (7.50%)	4	1/48 (2.08%)	1	1/46 (2.17%)	1	2/48 (4.17%)	2
Enuresis * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Irritability * 1	0/40 (0.00%)	0	0/39 (0.00%)	0	1/40 (2.50%)	1	3/48 (6.25%)	3	2/46 (4.35%)	2	1/48 (2.08%)	1
Negativism * 1	1/40 (2.50%)	1	2/39 (5.13%)	3	0/40 (0.00%)	0	0/48 (0.00%)	0	0/46 (0.00%)	0	0/48 (0.00%)	0
Renal and urinary disorders
Urinary incontinence * 1	0/40 (0.00%)	0	2/39 (5.13%)	2	1/40 (2.50%)	1	0/48 (0.00%)	0	0/46 (0.00%)	0	1/48 (2.08%)	1
Respiratory, thoracic and mediastinal disorders
Cough * 1	2/40 (5.00%)	2	1/39 (2.56%)	1	1/40 (2.50%)	1	1/48 (2.08%)	1	2/46 (4.35%)	2	3/48 (6.25%)	3
Rhinorrhoea * 1	1/40 (2.50%)	1	2/39 (5.13%)	2	1/40 (2.50%)	1	0/48 (0.00%)	0	3/46 (6.52%)	3	1/48 (2.08%)	1
Skin and subcutaneous tissue disorders
Rash * 1	1/40 (2.50%)	2	2/39 (5.13%)	2	2/40 (5.00%)	2	1/48 (2.08%)	1	0/46 (0.00%)	0	4/48 (8.33%)	4
1 Term from vocabulary, MedDRA v 19.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

The full results posting consists of the pooled analysis 1 and 2 of the studies with study ID ZX008-1501 and ZX008-1502. Pooled analysis 1 is referenced as Study 1 in the respective statistical analysis plan (SAP) and corresponding clinical study report (CSR). Pooled analysis 2 is referenced as Study 2 in the respective SAP and, due to the timing of regulatory submissions, Study 3 in the corresponding CSR and in this results posting.

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 of Results:

Sullivan J, Lagae L, Cross JH, Devinsky O, Guerrini R, Knupp KG, Laux L, Nikanorova M, Polster T, Talwar D, Ceulemans B, Nabbout R, Farfel GM, Galer BS, Gammaitoni AR, Lock M, Agarwal A, Scheffer IE; FAiRE DS Study Group. Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial. Epilepsia. 2023 Oct;64(10):2653-2666. doi: 10.1111/epi.17737. Epub 2023 Aug 17.

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.

Sullivan J, Specchio N, Devinsky O, Auvin S, Perry MS, Strzelczyk A, Gil-Nagel A, Dai D, Galer BS, Gammaitoni AR. Fenfluramine significantly reduces day-to-day seizure burden by increasing number of seizure-free days and time between seizures in patients with Dravet syndrome: A time-to-event analysis. Epilepsia. 2022 Jan;63(1):130-138. doi: 10.1111/epi.17106. Epub 2021 Oct 22.

Lagae L, Sullivan J, Knupp K, Laux L, Polster T, Nikanorova M, Devinsky O, Cross JH, Guerrini R, Talwar D, Miller I, Farfel G, Galer BS, Gammaitoni A, Mistry A, Morrison G, Lock M, Agarwal A, Lai WW, Ceulemans B; FAiRE DS Study Group. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2019 Dec 21;394(10216):2243-2254. doi: 10.1016/S0140-6736(19)32500-0. Epub 2019 Dec 17.

Sullivan J, Perry MS, Wheless JW, Galer B, Gammaitoni A. Fenfluramine responder analyses and numbers needed to treat: Translating epilepsy trial data into clinical practice. Eur J Paediatr Neurol. 2021 Mar;31:10-14. doi: 10.1016/j.ejpn.2021.01.005. Epub 2021 Jan 22.

• Responsible Party: UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )
• ClinicalTrials.gov Identifier: NCT02682927
• Obsolete Identifiers: NCT02826863
• Other Study ID Numbers: ZX008-1501; ZX008-1502 ( Other Identifier: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )
• First Submitted: February 5, 2016
• First Posted: February 17, 2016
• Results First Submitted: June 28, 2022
• Results First Posted: October 19, 2022
• Last Update Posted: September 28, 2023