Phase 3 N=296 Randomized Quadruple-blind Treatment

A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome

Lennox Gastaut Syndrome

Bottom Line

View on ClinicalTrials.gov: NCT03355209 ↗

Enrolled (actual)

296

Serious AEs

11.7%

Results posted

Jul 2025

Primary outcome: Primary: Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group — -7.59; -26.49; -17.89; -34.52 percent change — p=0.0008

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: ZX008 0.2 or 0.8 mg/kg/day (Drug); Matching Placebo (Drug)
Age: Pediatric, Adult · 2+ yrs
Sex: All
Sponsor: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
Primary completion: May 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group	-7.59; -26.49; -17.89; -34.52	0.0008 sig
PRIMARY Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	83.0; 96.9	—
PRIMARY Part 2: Percentage of Participants With Serious TEAEs	16.6; 18.8	—
SECONDARY Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/Day Group Compared to the Placebo Group	-7.59; -14.16; -17.89; -14.12	0.1460
SECONDARY Part 1: Percentage of Participants Who Achieve a >=50% Reduction From Baseline in the Frequency of Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	10.3; 28.1; 25.3; 9.1; 36.4; 36.4	0.0051 sig
SECONDARY Part 1: Percentage of Participants Who Achieve Improvement (Minimally, Much or Very Much Improved) in the CGI-I Scale as Assessed by Principal Investigator Comparing ZX008 0.8 and 0.2 mg/kg/Day Groups Independently Versus Placebo	33.8; 44.7; 48.8; 9.1; 45.5; 72.7	0.1565
SECONDARY Part 1: Percent Change From Baseline in Frequency of All Seizures That Typically Result in Drops in T+M, Whether ESC-confirmed as Drop or Not in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	-8.43; -11.75; -26.28; -17.89; -14.12; -34.04	—
SECONDARY Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	-8.43; -11.75; -26.28; -17.89; -14.12; -34.04	—
SECONDARY Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	0.00; 0.00; 0.00; -7.16; 0.00; 0.00	—
SECONDARY Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	-9.40; -23.55; -21.70; -17.69; -20.41; -13.85	—
SECONDARY Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) Between Baseline and the Maintenance Period	-7.28; -18.63; -27.16; -18.18; -12.88; -45.07	—
SECONDARY Part 1: Percent Change From Baseline in the Frequency of Seizures That Typically Result in Drops in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	-9.37; -17.30; -26.30; -18.18; -12.88; -46.88	—
SECONDARY Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	-10.21; -17.30; -28.33; -18.18; -12.88; -46.88	—
SECONDARY Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	-0.04; -0.13; 0.00; -4.00; 0.00; 0.00	—
SECONDARY Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	-9.49; -27.63; -23.34; -18.18; -20.33; -17.68	—
SECONDARY Part 1: Percent Change From Baseline in Frequency of Countable Seizures That do Not Result in Drops (ESC Confirmed)	-26.92; -31.32; -22.68; -23.38; 0.27; -22.99	—
SECONDARY Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops	37.9; 34.8; 21.8; 36.4; 27.3; 9.1	—
SECONDARY Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops	35.6; 36.0; 20.7; 36.4; 27.3; 9.1	—
SECONDARY Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures	34.5; 38.2; 20.7; 36.4; 27.3; 9.1	—
SECONDARY Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops	35.7; 34.2; 34.4; 25.0; 57.1; 44.4	—
SECONDARY Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures	36.8; 32.6; 28.7; 27.3; 27.3; 36.4	—
SECONDARY Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures	33.3; 34.4; 36.8; 25.0; 57.1; 37.5	—
SECONDARY Part 1: Change From Baseline in Number of Seizure-free Days During T+M and M Period	0.27; 0.00; 0.29; 0.00; 0.38; 6.65	—
SECONDARY Part 1: Duration of Longest Interval (Days) Between Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo	5.00; 4.00; 5.00; 4.00; 4.00; 6.00	—
SECONDARY Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver	2.4; 5.9; 9.9; 9.1; 10.0; 9.1	—
SECONDARY Part 1: Percentage of Participants With TEAEs	80.5; 78.7; 89.7; 72.7; 90.9; 63.6	—
SECONDARY Part 1: Percentage of Participants With Serious TEAEs	4.6; 4.5; 11.5; 9.1; 9.1; 0	—
SECONDARY Part 1: Maximum Observed Plasma Concentration of Fenfluramine and Norfenfluramine Determined Directly From the Concentration Time Profile [Cmax] at Steady State	11.9; 44.8; 9.04; 28.9	—
SECONDARY Part 1: Minimum Observed Plasma Concentration of Fenfluramine and Norfenfluramine at Steady State Determined Directly From the Concentration-time Profile [Cmin] at Steady State	8.19; 31.8; 8.23; 26.2	—
SECONDARY Part 1: Area Under the Concentration-time Curve of Fenfluramine and Norfenfluramine From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State	246; 933; 209; 667	—
SECONDARY Part 2: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) in OLE Period	-29.53; -43.42	—
SECONDARY Part 2: Percent Change From Baseline in the Frequency of All Seizures That Typically Result in Drops Between Baseline and the OLE Period Whether ESC Confirmed as Drop or Not	-27.94; -43.78	—
SECONDARY Part 2: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in OLE Period	-28.18; -41.94	—
SECONDARY Part 2: Change From Baseline in the Frequency of All Countable Non-motor Seizures in OLE Period	0.00; 0.00	—
SECONDARY Part 2: Percent Change From Baseline in the Frequency of All Countable Seizures (ESC Confirmed or Not) in OLE Period	-28.83; -28.00	—
SECONDARY Part 2: Change From Baseline in the Frequency of All Countable Seizures That Did Not Result in Drops (ESC Confirmed) in OLE Period	-0.99; 0.00	—
SECONDARY Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)	31.5; 18.8; 68.5; 81.3; 55.6; 62.5	—
SECONDARY Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops	32.0; 21.9; 68.0; 78.1; 53.1; 65.6	—
SECONDARY Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures	29.5; 21.9; 70.5; 78.1; 54.8; 62.5	—
SECONDARY Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures	24.1; 37.5; 46.1; 31.3; 41.9; 25.0	—
SECONDARY Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures	30.3; 37.5; 69.7; 62.5; 53.1; 56.3	—
SECONDARY Part 2: Change From Baseline in Number of Seizure-free Days Per 28 Days (ESC Confirmed) in OLE Period	2.16; 4.24	—
SECONDARY Part 2: Change From Baseline in Duration of Longest Interval Between Seizures That Result in Drops (ESC Confirmed) in OLE Period	4.0; 6.0	—
SECONDARY Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator	2.5; 3.1; 15.3; 18.8; 25.8; 18.8	—
SECONDARY Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver	6.9; 9.4; 16.8; 12.5; 24.6; 28.1	—

Summary

This is a two-part, multicenter, double-blind, parallel-group, placebo controlled study to evaluate the effect of ZX008 when used as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with Lennox-Gastaut syndrome (LGS).

Eligibility Criteria

Key Inclusion Criteria

Male or non-pregnant, non-lactating female, age 2 to 35 years, inclusive as of the day of the Screening Visit.
Clinical diagnosis of Lennox-Gastaut syndrome, where seizures that result in drops are not completely controlled by current antiepileptic treatments.
Onset of seizures at 11 years of age or younger.
Abnormal cognitive development.
Must be receiving at least 1 concomitant AED and up to 4 concomitant anti-epileptic treatments.

Key Exclusion Criteria

Etiology of seizures is a degenerative neurological disease.
History of hemiclonic seizures in the first year of life.
Subject only has drop seizures in clusters, where individual seizures cannot be counted reliably.
Pulmonary arterial hypertension.
Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
Receiving concomitant therapy with: centrally-acting anorectic agents; monoamineoxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine.
Taking felbamate for less than 1 year prior to screening and/or does not have stable liver function and hematology laboratory tests, and/or the dose has not been stable for at least 60 days prior to the Screening Visit.
Currently receiving an investigational product.
Institutionalized in a general nursing home (ie, in a facility that does not specialize in epilepsy care).
A clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03355209). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.