A Phase 3 interventional study of ZX008 0.2 or 0.8 mg/kg/day and Matching Placebo in Lennox Gastaut Syndrome, sponsored by Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.. Completed at 72 sites in 14 countries. Open to participants aged 2 Years to 35 Years. Per ClinicalTrials.gov, last updated 2025-07-03.
Sponsored by Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. (part of UCB S.A.) · Phase 3, Interventional, and Treatment
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Among 38 studies in Lennox Gastaut Syndrome with a site in United States — 7 open to participants now, 10 under way, 4 of them phase 3. Lennox Gastaut Syndrome · United States.
Among the 38 studies in Lennox Gastaut Syndrome with a site in United States, this one is the 5th largest by enrollment of the 32 interventional ones that give a count, is one of 2 that started in 2017, is one of 16 in phase 3, and was the 12th registered.
68 studies on the registry are indexed under Lennox Gastaut Syndrome; 13 are open to participants now.
Browse Lennox Gastaut Syndrome studies →7 of the 38 studies in Lennox Gastaut Syndrome with a site in United States are open now. Recruiting first, the newest first:
Epygenix · Sites in United States, China, Hungary and 7 more countries
Ages 2–55
SK Life Science, Inc. · Sites in United States, Argentina, Australia and 13 more countries
Ages 4–55
University of Chicago · Sites in United States
Ages 2–35
Byteflies · Sites in United States
Ages 3+
Longboard Pharmaceuticals · Sites in United States, Australia, Belgium and 14 more countries
Ages 2–66
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 4 Lennox Gastaut Syndrome studies recruiting now, none set no upper age limit and 4 stop at 75 or younger; 3 take children under 18; none take healthy volunteers.
This study: 2 Years to 35 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
38 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 7 · Phase 2 7 · Phase 3 16 · Phase 4 2
First in 1992; this study’s year is marked. 2 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 296 is above the median of 40 across 49 interventional studies indexed under Lennox Gastaut Syndrome.
Median enrollment 52 across the 32 interventional studies, 394 across the 4 observational. Of the 26 that completed or were terminated, 15 (58%) have results posted.
This tab as a report to print or save as PDF → With an account.
29 of 38 have an industry lead sponsor. The 10 most frequent:
This study is registered under Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc., one of the names counted as UCB S.A.. Under that name alone:
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. is the lead sponsor of 6 studies on the registry; none are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 5 (83%) have results posted.
UCB S.A. has 3 studies filed under Lennox Gastaut Syndrome — fewer than ten, so there is no comparison to draw.
5 of the studies in Lennox Gastaut Syndrome with a site in United States that are under way reach primary completion within a year, 2 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT05219617Phase 3SK Life Science, Inc.Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults | 2027-02 |
| NCT06908226Phase 3Longboard PharmaceuticalsA Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE) | 2027-11-11 |
| NCT05339126NeuroPaceRNS System LGS Feasibility Study | 2026-11-30 |
| NCT06738732Alexander RotenbergCBD Delivery with the A-Synaptic GT4 Transdermal Delivery System in with Dravet Syndrome And/or Lennox-Gastaut Syndrome | 2027-01 |
| NCT05044819Jazz PharmaceuticalsAssessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution | 2027-08-01 |
Add all 5 to your calendar (.ics) → With an account.
Among the 38 studies in Lennox Gastaut Syndrome with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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).
Key Inclusion Criteria:
Key Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Part 1: ZX008 is supplied as an oral solution. Subjects will be randomized to receive 1 of 2 doses of ZX008 0.2 mg/kg/day or 0.8 mg/kg/day.
Drug: ZX008 0.2 or 0.8 mg/kg/day
Part 1: Matching ZX008 placebo is supplied as an oral solution.
Drug: Matching Placebo
Part 2: ZX008 is supplied as an oral solution. Study medication will be administered twice a day (BID) in equally divided doses.
Drug: ZX008 0.2 or 0.8 mg/kg/day
Drug page: Fenfluramine
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride. The product is sugar free and is intended to be compatible with a Ketogenic Diet.
Placebo will be administered twice a day (BID) in equally divided doses.
Also known as: Placebo Comparator
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2.
Time frame: From Part 2 Baseline until end of the OLE Period (up to 72 months)
Part 2: Percentage of Participants With Serious TEAEs
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
Time frame: From Part 2 Baseline until end of the OLE Period (up to 72 months)
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/Day Group Compared to the Placebo Group
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieve a >=50% Reduction From Baseline in the Frequency of Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. Participants who achieved a \>=50% reduction from Baseline in the DSF, ie, a decrease in DSF of at least 50 percentage points per 28 days during Titration and Maintenance Period.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieve Improvement (Minimally, Much or Very Much Improved) in the CGI-I Scale as Assessed by Principal Investigator Comparing ZX008 0.8 and 0.2 mg/kg/Day Groups Independently Versus Placebo
Clinical Global Impression - Improvement (CGI-I) scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Time frame: At Day 99 (Visit 12)
Part 1: Percent Change From Baseline in Frequency of All Seizures That Typically Result in Drops in T+M, Whether ESC-confirmed as Drop or Not in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Seizures that typically result in drops included all: generalized tonic-clonic seizures \[GTC\], secondarily generalized tonic-clonic \[SGTC\], tonic seizures \[TS\], atonic seizures \[AS\], and tonic/atonic seizures \[TA\], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures \[CS\], hemiclonic seizures \[HS\], and focal seizures \[FS\] with clearly observable signs.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) Between Baseline and the Maintenance Period
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of Seizures That Typically Result in Drops in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC,TS, AS, TA, CS, HS, and FS with clearly observable signs.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Time frame: During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in Frequency of Countable Seizures That do Not Result in Drops (ESC Confirmed)
Non-drop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each participant as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
Countable non-motor seizures include: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Change From Baseline in Number of Seizure-free Days During T+M and M Period
A day with no seizures leading to a drop was defined as a day for which electronic (e) diary data were available and no drop seizures were reported. The total number of drop seizure-free days was calculated per 28 days for Baseline and for T+M.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Duration of Longest Interval (Days) Between Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
The longest interval between seizures leading to drops were obtained from the eDiary entries in Titration and Maintenance Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
Time frame: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved, 2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Time frame: At Days 15, 43, 71 and 99
Part 1: Percentage of Participants With TEAEs
Adverse events were defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A TEAE in Part 1 was defined as any AE that, based on start date information, occurred after the first dose of study drug in Part 1, but not on or after the first dose of study drug in Part 2.
Time frame: Baseline up to 14 weeks + Taper/Transition (2 weeks)
Part 1: Percentage of Participants With Serious TEAEs
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
Time frame: Baseline up to 14 weeks + Taper/Transition (2 weeks)
Part 1: Maximum Observed Plasma Concentration of Fenfluramine and Norfenfluramine Determined Directly From the Concentration Time Profile [Cmax] at Steady State
Cmax is the maximum plasma concentration determined directly from the concentration time profile.
Time frame: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 1: Minimum Observed Plasma Concentration of Fenfluramine and Norfenfluramine at Steady State Determined Directly From the Concentration-time Profile [Cmin] at Steady State
Cmin is the minimum plasma concentration determined directly from the concentration-time profile.
Time frame: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 1: Area Under the Concentration-time Curve of Fenfluramine and Norfenfluramine From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State
AUC0-24 is the area under the concentration-time curve from time 0 to 24 hours.
Time frame: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 2: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) in OLE Period
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Seizures That Typically Result in Drops Between Baseline and the OLE Period Whether ESC Confirmed as Drop or Not
Seizures that typically result in drops included all: generalized tonic-clonic seizures \[GTC\], secondarily generalized tonic-clonic \[SGTC\], tonic seizures \[TS\], atonic seizures \[AS\], and tonic/atonic seizures \[TA\], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in OLE Period
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures \[CS\], hemiclonic seizures \[HS\], and focal seizures \[FS\] with clearly observable signs.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in the Frequency of All Countable Non-motor Seizures in OLE Period
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Countable Seizures (ESC Confirmed or Not) in OLE Period
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in the Frequency of All Countable Seizures That Did Not Result in Drops (ESC Confirmed) in OLE Period
Nondrop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each subject as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Time frame: From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in Number of Seizure-free Days Per 28 Days (ESC Confirmed) in OLE Period
A day with no seizures leading to a drop was defined as a day for which ediary data were available and no drop seizures were reported.
Time frame: From Part 2 Baseline until end of OLE Period (up to 72 months)
Part 2: Change From Baseline in Duration of Longest Interval Between Seizures That Result in Drops (ESC Confirmed) in OLE Period
The longest interval between seizures leading to drops were obtained from the eDiary entries in OLE Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
Time frame: From Part 2 Baseline until end of the OLE Period (up to 72 months)
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Time frame: At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Time frame: At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
The study started to enroll participants in November 2017 and concluded in May 2024. Cohort A included participants enrolled at sites in North America, Europe, and Australia. Cohort B included participants enrolled at sites in Japan only.
| Milestone | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Started | 87 | 89 | 87 | 11 | 11 | 11 |
| Completed | 86 | 83 | 81 | 11 | 10 | 11 |
| Not completed | 1 | 6 | 6 | 0 | 1 | 0 |
| Withdrew: Adverse event | 0 | 4 | 4 | 0 | 1 | 0 |
| Withdrew: Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Physician decision | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 | 1 | 0 | 0 | 0 |
| Milestone | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Started | 86 | 83 | 78 | 11 | 10 | 11 |
| Completed | 61 | 51 | 46 | 5 | 1 | 5 |
| Not completed | 25 | 32 | 32 | 6 | 9 | 6 |
| Withdrew: Adverse event | 5 | 5 | 3 | 0 | 1 | 1 |
| Withdrew: Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Lack of efficacy | 13 | 21 | 23 | 0 | 0 | 1 |
| Withdrew: Switching to commercial zx008 | 0 | 0 | 0 | 5 | 6 | 3 |
| Withdrew: Withdrawal by subject | 6 | 5 | 4 | 0 | 2 | 0 |
| Withdrew: Physician decision | 0 | 0 | 0 | 1 | 0 | 1 |
| Withdrew: Rollover into zx008-1900 | 1 | 0 | 2 | 0 | 0 | 0 |
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|
| 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 (-100.0 to 557.1) | -26.49 (-95.2 to 402.1) | -17.89 (-97.3 to 61.8) | -34.52 (-69.4 to 45.5) |
An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 83.0 | 96.9 |
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Part 2: Percentage of Participants With Serious TEAEs | 16.6 | 18.8 |
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day |
|---|---|---|---|---|
| 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 (-100.0 to 557.1) | -14.16 (-100.0 to 3307.3) | -17.89 (-97.3 to 61.8) | -14.12 (-95.6 to 66.4) |
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. Participants who achieved a \>=50% reduction from Baseline in the DSF, ie, a decrease in DSF of at least 50 percentage points per 28 days during Titration and Maintenance Period.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 |
Clinical Global Impression - Improvement (CGI-I) scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 |
Seizures that typically result in drops included all: generalized tonic-clonic seizures \[GTC\], secondarily generalized tonic-clonic \[SGTC\], tonic seizures \[TS\], atonic seizures \[AS\], and tonic/atonic seizures \[TA\], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-100.0 to 557.1) | -11.75 (-100.0 to 3307.3) | -26.28 (-95.2 to 402.1) | -17.89 (-97.3 to 61.8) | -14.12 (-95.6 to 66.4) | -34.04 (-69.4 to 45.5) |
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures \[CS\], hemiclonic seizures \[HS\], and focal seizures \[FS\] with clearly observable signs.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-80.8 to 497.8) | -11.75 (-100.0 to 3307.3) | -26.28 (-91.9 to 402.1) | -17.89 (-97.3 to 61.8) | -14.12 (-95.6 to 174.1) | -34.04 (-69.4 to 45.5) |
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
| seizure frequency per 28 days | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-338.3 to 364.3) | 0.00 (-418.7 to 675.8) | 0.00 (-364.0 to 2952.7) | -7.16 (-30.3 to 13.1) | 0.00 (-32.3 to 104.8) | 0.00 (-61.6 to 209.5) |
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-85.4 to 497.8) | -23.55 (-100.0 to 882.1) | -21.70 (-91.9 to 224.9) | -17.69 (-97.2 to 61.8) | -20.41 (-87.1 to 826.2) | -13.85 (-64.9 to 63.8) |
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-100.0 to 516.7) | -18.63 (-100.0 to 964.0) | -27.16 (-100.0 to 643.3) | -18.18 (-99.4 to 66.7) | -12.88 (-100.0 to 239.4) | -45.07 (-77.8 to 52.2) |
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-100.0 to 516.7) | -17.30 (-100.0 to 964.0) | -26.30 (-100.0 to 643.3) | -18.18 (-99.4 to 66.7) | -12.88 (-100.0 to 239.4) | -46.88 (-77.8 to 52.2) |
Countable motor seizures included: GTC, SGTC,TS, AS, TA, CS, HS, and FS with clearly observable signs.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-81.1 to 439.8) | -17.30 (-100.0 to 964.0) | -28.33 (-100.0 to 643.3) | -18.18 (-99.4 to 66.7) | -12.88 (-100.0 to 472.7) | -46.88 (-77.8 to 52.2) |
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
| seizure frequency per 28 days | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-340.6 to 362.3) | -0.13 (-442.3 to 588.1) | 0.00 (-368.3 to 3219.3) | -4.00 (-30.7 to 15.3) | 0.00 (-37.2 to 192.0) | 0.00 (-86.8 to 250.7) |
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (-85.7 to 439.8) | -27.63 (-100.0 to 211.1) | -23.34 (-100.0 to 254.5) | -18.18 (-99.5 to 66.7) | -20.33 (-95.7 to 1626.7) | -17.68 (-72.3 to 80.5) |
Non-drop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each participant as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA.
| percent change | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Part 1: Percent Change From Baseline in Frequency of Countable Seizures That do Not Result in Drops (ESC Confirmed) | -26.92 (-100.0 to 5070.3) | -31.32 (-100.0 to 571.8) | -22.68 (-100.0 to 481.3) | -23.38 (-96.9 to 657.1) | 0.27 (-32.3 to 2915.4) | -22.99 (-85.7 to 138.8) |
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Worsening or No Change (T+M) | 37.9 | 34.8 | 21.8 | 36.4 | 27.3 | 9.1 |
| > 0% reduction (T+M) | 62.1 | 65.2 | 78.2 | 63.6 | 72.7 | 90.9 |
| >= 25% reduction (T+M) | 31.0 | 47.2 | 51.7 | 36.4 | 36.4 | 63.6 |
| >= 50% reduction (T+M) | 10.3 | 28.1 | 25.3 | 9.1 | 36.4 | 36.4 |
| >= 75% reduction (T+M) | 4.6 | 10.1 | 8.0 | 9.1 | 9.1 | 0 |
| 100% reduction (T+M) | 1.1 | 1.1 | 0 | 0 | 0 | 0 |
| Near Seizure free (T+M) | 1.1 | 2.2 | 1.1 | 0 | 0 | 0 |
| Worsening or No Change (M) | 40.2 | 35.2 | 20.9 | 36.4 | 27.3 | 9.1 |
| > 0% reduction (M) | 59.8 | 64.8 | 79.1 | 63.6 | 72.7 | 90.9 |
| >= 25% reduction (M) | 33.3 | 46.6 | 53.5 | 36.4 | 36.4 | 72.7 |
| >= 50% reduction (M) | 12.6 | 31.8 | 31.4 | 9.1 | 36.4 | 36.4 |
| >= 75% reduction (M) | 3.4 | 11.4 | 14.0 | 9.1 | 9.1 | 9.1 |
| 100% reduction (M) | 1.1 | 3.4 | 2.3 | 0 | 9.1 | 0 |
| Near Seizure free (M) | 1.1 | 4.5 | 2.3 | 9.1 | 9.1 | 0 |
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Worsening or No Change (T+M) | 35.6 | 36.0 | 20.7 | 36.4 | 27.3 | 9.1 |
| > 0% reduction (T+M) | 64.4 | 64.0 | 79.3 | 63.6 | 72.7 | 90.9 |
| >= 25% reduction (T+M) | 31.0 | 46.1 | 50.6 | 36.4 | 36.4 | 63.6 |
| >= 50% reduction (T+M) | 9.2 | 27.0 | 26.4 | 9.1 | 36.4 | 36.4 |
| >= 75% reduction (T+M) | 3.4 | 9.0 | 8.0 | 9.1 | 9.1 | 0 |
| 100% reduction (T+M) | 1.1 | 1.1 | 0 | 0 | 0 | 0 |
| Near Seizure free (T+M) | 1.1 | 1.1 | 1.1 | 0 | 0 | 0 |
| Worsening or No Change (M) | 37.9 | 37.5 | 19.8 | 36.4 | 27.3 | 9.1 |
| > 0% reduction (M) | 62.1 | 62.5 | 80.2 | 63.6 | 72.7 | 90.9 |
| >= 25% reduction (M) | 33.3 | 45.5 | 52.3 | 36.4 | 36.4 | 72.7 |
| >= 50% reduction (M) | 10.3 | 30.7 | 31.4 | 9.1 | 36.4 | 36.4 |
| >= 75% reduction (M) | 2.3 | 10.2 | 12.8 | 9.1 | 9.1 | 9.1 |
| 100% reduction (M) | 1.1 | 2.3 | 2.3 | 0 | 9.1 | 0 |
| Near Seizure free (M) | 1.1 | 2.3 | 2.3 | 9.1 | 9.1 | 0 |
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Worsening or No Change (T+M) | 34.5 | 38.2 | 20.7 | 36.4 | 27.3 | 9.1 |
| > 0% reduction (T+M) | 65.5 | 61.8 | 79.3 | 63.6 | 72.7 | 90.9 |
| >= 25% reduction (T+M) | 33.3 | 44.9 | 50.6 | 36.4 | 36.4 | 63.6 |
| >= 50% reduction (T+M) | 9.2 | 24.7 | 25.3 | 9.1 | 36.4 | 36.4 |
| >= 75% reduction (T+M) | 2.3 | 9.0 | 6.9 | 9.1 | 9.1 | 0 |
| 100% reduction (T+M) | 0 | 1.1 | 0 | 0 | 0 | 0 |
| Near Seizure free (T+M) | 0 | 1.1 | 0 | 0 | 0 | 0 |
| Worsening or No Change (M) | 36.8 | 38.6 | 18.6 | 36.4 | 27.3 | 9.1 |
| > 0% reduction (M) | 63.2 | 61.4 | 81.4 | 63.6 | 72.7 | 90.9 |
| >= 25% reduction (M) | 34.5 | 45.5 | 53.5 | 36.4 | 36.4 | 72.7 |
| >= 50% reduction (M) | 10.3 | 28.4 | 26.7 | 9.1 | 36.4 | 36.4 |
| >= 75% reduction (M) | 1.1 | 11.4 | 10.5 | 9.1 | 9.1 | 9.1 |
| 100% reduction (M) | 0 | 2.3 | 1.2 | 0 | 9.1 | 0 |
| Near Seizure free (M) | 0 | 2.3 | 1.2 | 9.1 | 9.1 | 0 |
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Worsening or No Change (T+M) | 35.7 | 34.2 | 34.4 | 25.0 | 57.1 | 44.4 |
| > 0% reduction (T+M) | 64.3 | 65.8 | 65.6 | 75.0 | 42.9 | 55.6 |
| >= 25% reduction (T+M) | 51.4 | 53.4 | 46.9 | 50.0 | 14.3 | 44.4 |
| >= 50% reduction (T+M) | 30.0 | 43.8 | 32.8 | 25.0 | 0 | 22.2 |
| >= 75% reduction (T+M) | 12.9 | 26.0 | 12.5 | 12.5 | 0 | 11.1 |
| 100% reduction (T+M) | 2.9 | 5.5 | 4.7 | 0 | 0 | 0 |
| Near Seizure free (T+M) | 2.9 | 9.6 | 7.8 | 0 | 0 | 0 |
| Worsening or No Change (M) | 31.4 | 33.3 | 34.9 | 25.0 | 57.1 | 44.4 |
| > 0% reduction (M) | 68.6 | 66.7 | 65.1 | 75.0 | 42.9 | 55.6 |
| >= 25% reduction (M) | 54.3 | 56.9 | 49.2 | 50.0 | 14.3 | 44.4 |
| >= 50% reduction (M) | 31.4 | 44.4 | 33.3 | 25.0 | 0 | 22.2 |
| >= 75% reduction (M) | 17.1 | 29.2 | 17.5 | 12.5 | 0 | 11.1 |
| 100% reduction (M) | 5.7 | 9.7 | 6.3 | 12.5 | 0 | 0 |
| Near Seizure free (M) | 7.1 | 13.9 | 9.5 | 12.5 | 0 | 0 |
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Worsening or No Change (T+M) | 36.8 | 32.6 | 28.7 | 27.3 | 27.3 | 36.4 |
| > 0% reduction (T+M) | 63.2 | 67.4 | 71.3 | 72.7 | 72.7 | 63.6 |
| >= 25% reduction (T+M) | 35.6 | 48.3 | 46.0 | 27.3 | 27.3 | 45.5 |
| >= 50% reduction (T+M) | 11.5 | 22.5 | 20.7 | 9.1 | 27.3 | 27.3 |
| >= 75% reduction (T+M) | 3.4 | 6.7 | 4.6 | 9.1 | 9.1 | 0 |
| 100% reduction (T+M) | 0 | 1.1 | 0 | 0 | 0 | 0 |
| Near Seizure free (T+M) | 0 | 1.1 | 0 | 0 | 0 | 0 |
| Worsening or No Change (M) | 34.5 | 33.0 | 27.9 | 27.3 | 27.3 | 27.3 |
| > 0% reduction (M) | 65.5 | 67.0 | 72.1 | 72.7 | 72.7 | 72.7 |
| >= 25% reduction (M) | 34.5 | 51.1 | 47.7 | 27.3 | 27.3 | 45.5 |
| >= 50% reduction (M) | 13.8 | 28.4 | 24.4 | 9.1 | 27.3 | 27.3 |
| >= 75% reduction (M) | 3.4 | 9.1 | 7.0 | 9.1 | 9.1 | 0 |
| 100% reduction (M) | 0 | 1.1 | 1.2 | 0 | 0 | 0 |
| Near Seizure free (M) | 0 | 1.1 | 1.2 | 9.1 | 0 | 0 |
Countable non-motor seizures include: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Worsening or No Change (T+M) | 33.3 | 34.4 | 36.8 | 25.0 | 57.1 | 37.5 |
| > 0% reduction (T+M) | 66.7 | 65.6 | 63.2 | 75.0 | 42.9 | 62.5 |
| >= 25% reduction (T+M) | 52.4 | 56.3 | 43.9 | 50.0 | 14.3 | 37.5 |
| >= 50% reduction (T+M) | 30.2 | 48.4 | 35.1 | 25.0 | 0 | 25.0 |
| >= 75% reduction (T+M) | 14.3 | 32.8 | 12.3 | 12.5 | 0 | 0 |
| 100% reduction (T+M) | 3.2 | 6.3 | 3.5 | 0 | 0 | 0 |
| Near Seizure free (T+M) | 3.2 | 14.1 | 5.3 | 0 | 0 | 0 |
| Worsening or No Change (M) | 30.2 | 30.2 | 33.9 | 12.5 | 57.1 | 37.5 |
| > 0% reduction (M) | 69.8 | 69.8 | 66.1 | 87.5 | 42.9 | 62.5 |
| >= 25% reduction (M) | 54.0 | 60.3 | 48.2 | 50.0 | 14.3 | 37.5 |
| >= 50% reduction (M) | 34.9 | 49.2 | 33.9 | 25.0 | 0 | 37.5 |
| >= 75% reduction (M) | 17.5 | 31.7 | 17.9 | 12.5 | 0 | 0 |
| 100% reduction (M) | 6.3 | 9.5 | 8.9 | 12.5 | 0 | 0 |
| Near Seizure free (M) | 7.9 | 15.9 | 10.7 | 12.5 | 0 | 0 |
A day with no seizures leading to a drop was defined as a day for which electronic (e) diary data were available and no drop seizures were reported. The total number of drop seizure-free days was calculated per 28 days for Baseline and for T+M.
| seizure free days per 28 days | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| T+M Period | 0.27 (-5.0 to 16.0) | 0.00 (-9.0 to 16.8) | 0.29 (-6.1 to 20.0) | 0.00 (-2.2 to 23.6) | 0.38 (-2.3 to 22.0) | 6.65 (-2.4 to 8.5) |
| M Period | 0.31 (-5.4 to 15.7) | 0.00 (-4.1 to 18.2) | 0.16 (-7.4 to 21.7) | -0.65 (-2.7 to 24.7) | 0.33 (-7.3 to 26.0) | 7.72 (-2.3 to 10.3) |
The longest interval between seizures leading to drops were obtained from the eDiary entries in Titration and Maintenance Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
| days | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 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 (1.0 to 39.0) | 4.00 (1.0 to 97.0) | 5.00 (1.0 to 89.0) | 4.00 (1.0 to 91.0) | 4.00 (1.0 to 32.0) | 6.00 (2.0 to 16.0) |
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved, 2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| 1=Very much improved (D15) | 2.4 | 5.9 | 9.9 | 9.1 | 10.0 | 9.1 |
| 2=Much improved (D15) | 4.7 | 15.3 | 21.0 | 18.2 | 10.0 | 18.2 |
| 3=Minimally improved (D15) | 31.8 | 27.1 | 39.5 | 9.1 | 30.0 | 27.3 |
| 4=No Change (D15) | 51.8 | 42.4 | 18.5 | 63.6 | 30.0 | 27.3 |
| 5=Minimally worse (D15) | 4.7 | 5.9 | 7.4 | 0 | 20.0 | 18.2 |
| 6=Much worse (D15) | 4.7 | 3.5 | 2.5 | 0 | 0 | 0 |
| 7=Very much worse (D15) | 0 | 0 | 1.2 | 0 | 0 | 0 |
| 1=Very much improved (D43) | 1.2 | 7.3 | 13.8 | 9.1 | 0 | 10.0 |
| 2=Much improved (D43) | 9.4 | 19.5 | 25.0 | 0 | 22.2 | 40.0 |
| 3=Minimally improved (D43) | 20.0 | 18.3 | 33.8 | 18.2 | 44.4 | 30.0 |
| 4=No Change (D43) | 60.0 | 39.0 | 17.5 | 63.6 | 33.3 | 0 |
| 5=Minimally worse (D43) | 5.9 | 11.0 | 5.0 | 9.1 | 0 | 20.0 |
| 6=Much worse (D43) | 2.4 | 4.9 | 5.0 | 0 | 0 | 0 |
| 7=Very much worse (D43) | 1.2 | 0 | 0 | 0 | 0 | 0 |
| 1=Very much improved (D71) | 2.4 | 4.0 | 10.7 | 9.1 | 0 | 0 |
| 2=Much improved (D71) | 6.1 | 20.0 | 28.0 | 0 | 22.2 | 11.1 |
| 3=Minimally improved (D71) | 24.4 | 16.0 | 33.3 | 18.2 | 22.2 | 55.6 |
| 4=No Change (D71) | 53.7 | 48.0 | 24.0 | 63.6 | 55.6 | 22.2 |
| 5=Minimally worse (D71) | 7.3 | 8.0 | 1.3 | 9.1 | 0 | 11.1 |
| 6=Much worse (D71) | 6.1 | 4.0 | 2.7 | 0 | 0 | 0 |
| 7=Very much worse (D71) | 0 | 0 | 0 | 0 | 0 | 0 |
| 1=Very much improved (D99) | 1.2 | 8.2 | 10.0 | 9.1 | 0 | 18.2 |
| 2=Much improved (D99) | 3.7 | 18.8 | 23.8 | 0 | 18.2 | 18.2 |
| 3=Minimally improved (D99) | 32.1 | 16.5 | 27.5 | 18.2 | 27.3 | 36.4 |
| 4=No Change (D99) | 53.1 | 37.6 | 27.5 | 63.6 | 45.5 | 27.3 |
| 5=Minimally worse (D99) | 7.4 | 8.2 | 5.0 | 0 | 9.1 | 0 |
| 6=Much worse (D99) | 2.5 | 7.1 | 5.0 | 9.1 | 0 | 0 |
| 7=Very much worse (D99) | 0 | 3.5 | 1.3 | 0 | 0 | 0 |
Adverse events were defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A TEAE in Part 1 was defined as any AE that, based on start date information, occurred after the first dose of study drug in Part 1, but not on or after the first dose of study drug in Part 2.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Part 1: Percentage of Participants With TEAEs | 80.5 | 78.7 | 89.7 | 72.7 | 90.9 | 63.6 |
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
| percentage of participants | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day |
|---|---|---|---|---|---|---|
| Part 1: Percentage of Participants With Serious TEAEs | 4.6 | 4.5 | 11.5 | 9.1 | 9.1 | 0 |
Cmax is the maximum plasma concentration determined directly from the concentration time profile.
| nanograms per milliliter (ng/mL) | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day |
|---|---|---|
| Fenfluramine | 11.9 ± 56.1 | 44.8 ± 47.0 |
| Norfenfluramine | 9.04 ± 53.4 | 28.9 ± 52.9 |
Cmin is the minimum plasma concentration determined directly from the concentration-time profile.
| ng/mL | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day |
|---|---|---|
| Fenfluramine | 8.19 ± 75.6 | 31.8 ± 60.8 |
| Norfenfluramine | 8.23 ± 61.3 | 26.2 ± 58.9 |
AUC0-24 is the area under the concentration-time curve from time 0 to 24 hours.
| nanograms*hour per milliliter (ng*h/mL) | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day |
|---|---|---|
| Fenfluramine | 246 ± 63.0 | 933 ± 52.1 |
| Norfenfluramine | 209 ± 56.3 | 667 ± 55.1 |
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
| percent change | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Part 2: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) in OLE Period | -29.53 (-100.0 to 2625.3) | -43.42 (-99.0 to 64.2) |
Seizures that typically result in drops included all: generalized tonic-clonic seizures \[GTC\], secondarily generalized tonic-clonic \[SGTC\], tonic seizures \[TS\], atonic seizures \[AS\], and tonic/atonic seizures \[TA\], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
| percent change | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| 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 (-100.0 to 2625.3) | -43.78 (-99.0 to 64.2) |
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures \[CS\], hemiclonic seizures \[HS\], and focal seizures \[FS\] with clearly observable signs.
| percent change | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Part 2: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in OLE Period | -28.18 (-100.0 to 2625.3) | -41.94 (-99.0 to 64.2) |
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
| seizure frequency per 28 days | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Part 2: Change From Baseline in the Frequency of All Countable Non-motor Seizures in OLE Period | 0.00 (-4257.2 to 1774.3) | 0.00 (-89.4 to 258.9) |
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
| percent change | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Part 2: Percent Change From Baseline in the Frequency of All Countable Seizures (ESC Confirmed or Not) in OLE Period | -28.83 (-100.0 to 606.1) | -28.00 (-99.1 to 83.3) |
Nondrop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each subject as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
| seizure frequency per 28 days | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| 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 (-4482.2 to 1774.3) | 0.00 (-89.4 to 258.9) |
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Worsening or No Change | 31.5 | 18.8 |
| > 0% | 68.5 | 81.3 |
| >= 25% | 55.6 | 62.5 |
| >= 50% | 32.8 | 43.8 |
| >= 75% | 12.4 | 21.9 |
| 100% | 1.2 | 0 |
| Near Seizure free | 1.7 | 0 |
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Worsening or No Change | 32.0 | 21.9 |
| > 0% | 68.0 | 78.1 |
| >= 25% | 53.1 | 65.6 |
| >= 50% | 29.9 | 43.8 |
| >= 75% | 11.2 | 21.9 |
| 100% | 0.8 | 0 |
| Near Seizure free | 1.2 | 0 |
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Worsening or No Change | 29.5 | 21.9 |
| > 0% | 70.5 | 78.1 |
| >= 25% | 54.8 | 62.5 |
| >= 50% | 29.9 | 40.6 |
| >= 75% | 9.1 | 21.9 |
| 100% | 0.4 | 0 |
| Near Seizure free | 0.8 | 0 |
Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Worsening or No Change | 24.1 | 37.5 |
| > 0% | 46.1 | 31.3 |
| >= 25% | 41.9 | 25.0 |
| >= 50% | 34.0 | 18.8 |
| >= 75% | 22.8 | 6.3 |
| 100% | 4.6 | 3.1 |
| Near Seizure free | 7.5 | 6.3 |
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Worsening or No Change | 30.3 | 37.5 |
| > 0% | 69.7 | 62.5 |
| >= 25% | 53.1 | 56.3 |
| >= 50% | 30.7 | 28.1 |
| >= 75% | 9.1 | 12.5 |
| 100% | 0.4 | 0 |
| Near Seizure free | 0.4 | 0 |
A day with no seizures leading to a drop was defined as a day for which ediary data were available and no drop seizures were reported.
| seizure free days per 28 days | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Part 2: Change From Baseline in Number of Seizure-free Days Per 28 Days (ESC Confirmed) in OLE Period | 2.16 (-23.0 to 27.8) | 4.24 (-3.6 to 24.5) |
The longest interval between seizures leading to drops were obtained from the eDiary entries in OLE Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
| days | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| Part 2: Change From Baseline in Duration of Longest Interval Between Seizures That Result in Drops (ESC Confirmed) in OLE Period | 4.0 (-10 to 360) | 6.0 (0 to 200) |
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| 1=Very much improved (OLE D1) | 2.5 | 3.1 |
| 2=Much improved (OLE D1) | 15.3 | 18.8 |
| 3=Minimally improved (OLE D1) | 25.8 | 18.8 |
| 4=No Change (OLE D1) | 48.3 | 56.3 |
| 5=Minimally worse (OLE D1) | 7.2 | 3.1 |
| 6=Much worse (OLE D1) | 0.8 | 0 |
| 7=Very much worse (OLE D1) | 0 | 0 |
| 1=Very much improved (OLE M1) | 4.4 | 9.4 |
| 2=Much improved (OLE M1) | 20.0 | 21.9 |
| 3=Minimally improved (OLE M1) | 32.4 | 37.5 |
| 4=No Change (OLE M1) | 34.2 | 31.3 |
| 5=Minimally worse (OLE M1) | 7.6 | 0 |
| 6=Much worse (OLE M1) | 1.3 | 0 |
| 7=Very much worse (OLE M1) | 0 | 0 |
| 1=Very much improved (OLE M2) | 5.5 | 6.5 |
| 2=Much improved (OLE M2) | 24.5 | 19.4 |
| 3=Minimally improved (OLE M2) | 34.1 | 35.5 |
| 4=No Change (OLE M2) | 27.7 | 32.3 |
| 5=Minimally worse (OLE M2) | 5.0 | 6.5 |
| 6=Much worse (OLE M2) | 3.2 | 0 |
| 7=Very much worse (OLE M2) | 0 | 0 |
| 1=Very much improved (OLE M3) | 7.2 | 6.9 |
| 2=Much improved (OLE M3) | 25.1 | 17.2 |
| 3=Minimally improved (OLE M3) | 36.2 | 55.2 |
| 4=No Change (OLE M3) | 21.7 | 20.7 |
| 5=Minimally worse (OLE M3) | 7.2 | 0 |
| 6=Much worse (OLE M3) | 2.4 | 0 |
| 7=Very much worse (OLE M3) | 0 | 0 |
| 1=Very much improved (OLE M6) | 8.2 | 3.4 |
| 2=Much improved (OLE M6) | 33.7 | 27.6 |
| 3=Minimally improved (OLE M6) | 31.0 | 34.5 |
| 4=No Change (OLE M6) | 20.1 | 27.6 |
| 5=Minimally worse (OLE M6) | 3.8 | 6.9 |
| 6=Much worse (OLE M6) | 3.3 | 0 |
| 7=Very much worse (OLE M6) | 0 | 0 |
| 1=Very much improved (OLE M9) | 9.0 | 3.6 |
| 2=Much improved (OLE M9) | 37.6 | 28.6 |
| 3=Minimally improved (OLE M9) | 27.1 | 28.6 |
| 4=No Change (OLE M9) | 18.8 | 35.7 |
| 5=Minimally worse (OLE M9) | 6.0 | 3.6 |
| 6=Much worse (OLE M9) | 1.5 | 0 |
| 7=Very much worse (OLE M9) | 0 | 0 |
| 1=Very much improved (OLE M12) | 9.7 | 0 |
| 2=Much improved (OLE M12) | 39.3 | 53.8 |
| 3=Minimally improved (OLE M12) | 26.2 | 23.1 |
| 4=No Change (OLE M12) | 18.6 | 19.2 |
| 5=Minimally worse (OLE M12) | 3.4 | 3.8 |
| 6=Much worse (OLE M12) | 2.8 | 0 |
| 7=Very much worse (OLE M12) | 0 | 0 |
| 1=Very much improved (Last Assessment) | 7.6 | 6.3 |
| 2=Much improved (Last Assessment) | 27.4 | 25.0 |
| 3=Minimally improved (Last Assessment) | 21.9 | 25.0 |
| 4=No Change (Last Assessment) | 28.3 | 40.6 |
| 5=Minimally worse (Last Assessment) | 7.2 | 3.1 |
| 6=Much worse (Last Assessment) | 7.6 | 0 |
| 7=Very much worse (Last Assessment) | 0 | 0 |
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
| percentage of participants | Part 2: Cohort A- Overall | Part 2: Cohort B- Overall |
|---|---|---|
| 1=Very much improved (OLE D1) | 6.9 | 9.4 |
| 2=Much improved (OLE D1) | 16.8 | 12.5 |
| 3=Minimally improved (OLE D1) | 24.6 | 28.1 |
| 4=No Change (OLE D1) | 40.1 | 43.8 |
| 5=Minimally worse (OLE D1) | 6.9 | 3.1 |
| 6=Much worse (OLE D1) | 3.9 | 3.1 |
| 7=Very much worse (OLE D1) | 0.9 | 0 |
| 1=Very much improved (OLE M1) | 7.1 | 12.5 |
| 2=Much improved (OLE M1) | 21.4 | 15.6 |
| 3=Minimally improved (OLE M1) | 32.1 | 31.3 |
| 4=No Change (OLE M1) | 29.5 | 40.6 |
| 5=Minimally worse (OLE M1) | 5.8 | 0 |
| 6=Much worse (OLE M1) | 4.0 | 0 |
| 7=Very much worse (OLE M1) | 0 | 0 |
| 1=Very much improved (OLE M2) | 7.3 | 12.9 |
| 2=Much improved (OLE M2) | 25.6 | 16.1 |
| 3=Minimally improved (OLE M2) | 32.0 | 41.9 |
| 4=No Change (OLE M2) | 25.6 | 22.6 |
| 5=Minimally worse (OLE M2) | 6.4 | 6.5 |
| 6=Much worse (OLE M2) | 2.3 | 0 |
| 7=Very much worse (OLE M2) | 0.9 | 0 |
| 1=Very much improved (OLE M3) | 9.7 | 13.8 |
| 2=Much improved (OLE M3) | 30.0 | 10.3 |
| 3=Minimally improved (OLE M3) | 29.5 | 37.9 |
| 4=No Change (OLE M3) | 19.3 | 37.9 |
| 5=Minimally worse (OLE M3) | 9.7 | 0 |
| 6=Much worse (OLE M3) | 0.5 | 0 |
| 7=Very much worse (OLE M3) | 1.4 | 0 |
| 1=Very much improved (OLE M6) | 13.4 | 10.3 |
| 2=Much improved (OLE M6) | 30.1 | 31.0 |
| 3=Minimally improved (OLE M6) | 27.4 | 34.5 |
| 4=No Change (OLE M6) | 23.1 | 20.7 |
| 5=Minimally worse (OLE M6) | 3.2 | 0 |
| 6=Much worse (OLE M6) | 2.2 | 3.4 |
| 7=Very much worse (OLE M6) | 0.5 | 0 |
| 1=Very much improved (OLE M9) | 13.4 | 14.3 |
| 2=Much improved (OLE M9) | 37.3 | 25.0 |
| 3=Minimally improved (OLE M9) | 26.1 | 21.4 |
| 4=No Change (OLE M9) | 14.2 | 32.1 |
| 5=Minimally worse (OLE M9) | 8.2 | 3.6 |
| 6=Much worse (OLE M9) | 0.7 | 3.6 |
| 7=Very much worse (OLE M9) | 0 | 0 |
| 1=Very much improved (OLE M12) | 16.8 | 19.2 |
| 2=Much improved (OLE M12) | 34.2 | 26.9 |
| 3=Minimally improved (OLE M12) | 26.8 | 46.2 |
| 4=No Change (OLE M12) | 14.8 | 3.8 |
| 5=Minimally worse (OLE M12) | 4.7 | 3.8 |
| 6=Much worse (OLE M12) | 2.0 | 0 |
| 7=Very much worse (OLE M12) | 0.7 | 0 |
| 1=Very much improved (Last Assessment) | 11.4 | 12.5 |
| 2=Much improved (Last Assessment) | 24.1 | 28.1 |
| 3=Minimally improved (Last Assessment) | 24.5 | 18.8 |
| 4=No Change (Last Assessment) | 25.3 | 28.1 |
| 5=Minimally worse (Last Assessment) | 9.3 | 9.4 |
| 6=Much worse (Last Assessment) | 3.4 | 3.1 |
| 7=Very much worse (Last Assessment) | 2.1 | 0 |
Collected over From Day 1 up to 72 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: Cohort A- Placebo | 0/87 (0%) | 4/87 (4.6%) | 60/87 (69%) |
| Part 1: Cohort A- ZX008 0.2 mg/kg/Day | 0/89 (0%) | 4/89 (4.5%) | 64/89 (71.9%) |
| Part 1: Cohort A- ZX008 0.8 mg/kg/Day | 1/87 (1.1%) | 10/87 (11.5%) | 68/87 (78.2%) |
| Part 2: Cohort A- Overall | 1/247 (0.4%) | 41/247 (16.6%) | 166/247 (67.2%) |
| Part 1: Cohort B- Placebo | 0/11 (0%) | 1/11 (9.1%) | 8/11 (72.7%) |
| Part 1: Cohort B- ZX008 0.2 mg/kg/Day | 0/11 (0%) | 1/11 (9.1%) | 10/11 (90.9%) |
| Part 1: Cohort B- ZX008 0.8 mg/kg/Day | 0/11 (0%) | 0/11 (0%) | 7/11 (63.6%) |
| Part 2: Cohort B- Overall | 0/32 (0%) | 6/32 (18.8%) | 30/32 (93.8%) |
| Event | Part 1: Cohort A- Placebo | Part 1: Cohort A- ZX008 0.2 mg/kg/Day | Part 1: Cohort A- ZX008 0.8 mg/kg/Day | Part 2: Cohort A- Overall | Part 1: Cohort B- Placebo | Part 1: Cohort B- ZX008 0.2 mg/kg/Day | Part 1: Cohort B- ZX008 0.8 mg/kg/Day | Part 2: Cohort B- Overall |
|---|---|---|---|---|---|---|---|---|
| SomnolenceNervous system disorders | 0/87 | 0/89 | 1/87 | 3/247 | 0/11 | 1/11 | 0/11 | 1/32 |
| Seizure clusterNervous system disorders | 0/87 | 0/89 | 0/87 | 0/247 | 1/11 | 0/11 | 0/11 | 2/32 |
| Change in seizure presentationNervous system disorders | 0/87 | 2/89 | 0/87 | 10/247 | 0/11 | 0/11 | 0/11 | 0/32 |
| Status epilepticusNervous system disorders | 1/87 | 0/89 | 3/87 | 8/247 | 0/11 | 0/11 | 0/11 | 0/32 |
| PneumoniaInfections and infestations | 0/87 | 1/89 | 2/87 | 5/247 | 0/11 | 0/11 | 0/11 | 1/32 |
| Dental cariesGastrointestinal disorders | 0/87 | 0/89 | 0/87 | 0/247 | 0/11 | 0/11 | 0/11 | 1/32 |
| Enterobacter bacteraemiaInfections and infestations | 0/87 | 0/89 | 0/87 | 0/247 | 0/11 | 0/11 | 0/11 | 1/32 |
| Facial bones fractureInjury, poisoning and procedural complications | 0/87 | 0/89 | 0/87 | 0/247 | 0/11 | 0/11 | 0/11 | 1/32 |
| Foreign body in gastrointestinal tractInjury, poisoning and procedural complications | 0/87 | 0/89 | 0/87 | 0/247 | 0/11 | 0/11 | 0/11 | 1/32 |
| SeizureNervous system disorders | 2/87 | 0/89 | 0/87 | 3/247 | 0/11 | 0/11 | 0/11 | 0/32 |
| Event | Part 1: Cohort A- Placebo | Part 1: Cohort A- ZX008 0.2 mg/kg/Day | Part 1: Cohort A- ZX008 0.8 mg/kg/Day | Part 2: Cohort A- Overall | Part 1: Cohort B- Placebo | Part 1: Cohort B- ZX008 0.2 mg/kg/Day | Part 1: Cohort B- ZX008 0.8 mg/kg/Day | Part 2: Cohort B- Overall |
|---|---|---|---|---|---|---|---|---|
| Corona virus infectionInfections and infestations | 0/87 | 0/89 | 0/87 | 2/247 | 0/11 | 0/11 | 0/11 | 12/32 |
| Decreased appetiteMetabolism and nutrition disorders | 13/87 | 18/89 | 32/87 | 39/247 | 2/11 | 3/11 | 3/11 | 4/32 |
| Weight decreasedInvestigations | 2/87 | 3/89 | 7/87 | 12/247 | 1/11 | 2/11 | 4/11 | 4/32 |
| SomnolenceNervous system disorders | 10/87 | 10/89 | 15/87 | 24/247 | 1/11 | 4/11 | 3/11 | 11/32 |
| NasopharyngitisInfections and infestations | 8/87 | 4/89 | 7/87 | 31/247 | 2/11 | 2/11 | 0/11 | 9/32 |
| DiarrhoeaGastrointestinal disorders | 4/87 | 10/89 | 10/87 | 13/247 | 0/11 | 3/11 | 2/11 | 5/32 |
| Blood prolactin increasedInvestigations | 1/87 | 0/89 | 3/87 | 9/247 | 0/11 | 1/11 | 0/11 | 8/32 |
| PyrexiaGeneral disorders | 11/87 | 11/89 | 9/87 | 25/247 | 1/11 | 0/11 | 0/11 | 7/32 |
| FatigueGeneral disorders | 11/87 | 8/89 | 16/87 | 33/247 | 0/11 | 0/11 | 0/11 | 0/32 |
| ConstipationGastrointestinal disorders | 5/87 | 5/89 | 8/87 | 18/247 | 0/11 | 0/11 | 0/11 | 5/32 |
Baseline characteristics refers to Safety Population which consisted of all randomized participants who received at least 1 dose of study drug.
| Age, Continuous(years) | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day | Total |
|---|---|---|---|---|---|---|---|
| Mean | 14.4 ± 7.71 | 13.4 ± 7.79 | 13.4 ± 7.28 | 18.5 ± 7.78 | 20.1 ± 7.79 | 18.5 ± 7.94 | 14.3 ± 7.76 |
| Age, Customized(Participants) | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day | Total |
|---|---|---|---|---|---|---|---|
| 2 - < 12 years | 32 | 41 | 37 | 2 | 3 | 2 | 117 |
| 12 - < 18 years | 29 | 23 | 25 | 5 | 2 | 3 | 87 |
| 18 - 35 years | 26 | 25 | 25 | 4 | 6 | 6 | 92 |
| Sex: Female, Male(Participants) | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day | Total |
|---|---|---|---|---|---|---|---|
| Female | 41 | 43 | 33 | 5 | 2 | 2 | 126 |
| Male | 46 | 46 | 54 | 6 | 9 | 9 | 170 |
| Race/Ethnicity, Customized(Participants) | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day | Total |
|---|---|---|---|---|---|---|---|
| White | 71 | 67 | 70 | 0 | 0 | 0 | 208 |
| Black or African American | 4 | 5 | 3 | 0 | 0 | 0 | 12 |
| Asian | 2 | 3 | 4 | 11 | 11 | 11 | 42 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Not Reported | 6 | 11 | 7 | 0 | 0 | 0 | 24 |
| Unknown | 2 | 2 | 2 | 0 | 0 | 0 | 6 |
| Multiple | 2 | 0 | 1 | 0 | 0 | 0 | 3 |
| Race/Ethnicity, Customized(Participants) | Cohort A: Placebo | Cohort A: ZX008 0.2 mg/kg/Day | Cohort A: ZX008 0.8 mg/kg/Day | Cohort B: Placebo | Cohort B: ZX008 0.2 mg/kg/Day | Cohort B: ZX008 0.8 mg/kg/Day | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 16 | 21 | 14 | 0 | 0 | 0 | 51 |
| Not Hispanic or Latino | 65 | 58 | 66 | 11 | 11 | 11 | 222 |
| Not Reported | 6 | 10 | 7 | 0 | 0 | 0 | 23 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
Supporting information: Study protocol, Statistical analysis plan, Clinical study report
Time frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
Access criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
Data sharing details ↗ · www.vivli.org
Ran from Nov 2017 to primary completion in May 2024, 77 months.
Results were first posted in Jul 2025, 1 year 1 month after primary completion.
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Studies of the drug tested here: Fenfluramine
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. →