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

Zogenix, Inc.412 enrolled

Overview

This is an international, multicenter, open-label, long-term safety study of ZX008 in subjects with Dravet syndrome, Lennox-Gastaut syndrome or epileptic encephalopathy

This is an international, multicenter, open-label, long-term safety study of ZX008 in patients with epileptic encephalopathy, including Dravet syndrome or Lennox-Gastaut syndrome. Subjects eligible for participation are those with Dravet syndrome who are currently enrolled in Study ZX008-1503, or those with Lennox-Gastaut syndrome who have successfully completed Study ZX008-1601-Part 2, and are candidates for continued treatment with ZX008 for an extended period of time, or those with Dravet syndrome, Lennox-Gastaut syndrome, or another epileptic encephalopathy who have completed participation in another Zogenix-sponsored study and have been invited to participate in this study.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

412

Conditions

Dravet Syndrome Lennox Gastaut Syndrome Epileptic Encephalopathy

Interventions

ZX008 (Fenfluramine Hydrochloride)DRUG

Fenfluramine hydrochloride provided in a concentration of 2.5 mg/mL.

Eligibility

Sex: ALLMin age: 2 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or nonpregnant, nonlactating female * Satisfactory completion of a core study * Has a rare seizure disorder, such as epileptic encephalopathy and has successfully completed another Zogenix-sponsored clinical trials with ZX008 * Subject's caregiver is willing and able to be compliant with study procedures, visit schedule and study drug accountability Exclusion Criteria: * Current cardiac valvulopathy or pulmonary hypertension that is clinically significant * Moderate or severe hepatic impairment * Receiving monoamine oxidase inhibitors, serotonin agonists, serotonin antagonists, and serotonin reuptake inhibitors within 14 days of receiving ZX008

Locations (71)

Outcomes

Primary Outcomes

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

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

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

Secondary Outcomes

Clinical Global Impression-Improvement in Participants, Subscale Global: Assessment by Parent/Caregiver

The Clinical Global Impression-Improvement (CGI-I) scale is used to assess the severity of illness and global improvement in patients. Global function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The global CGI-I assessment was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

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

Clinical Global Impression-Improvement in Participants, Subscale Global: Assessment by Investigator

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Global function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The global CGI-I assessment was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Data from ClinicalTrials.gov

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Ep0215 107

Tucson, Arizona, United States

Ep0215 144

Los Angeles, California, United States

Ep0215 108

San Diego, California, United States

Ep0215 101

San Francisco, California, United States

Ep0215 103

Aurora, Colorado, United States

Ep0215 115

Gulf Breeze, Florida, United States

Ep0215 104

Miami, Florida, United States

Ep0215 141

Orlando, Florida, United States

Ep0215 121

Winter Park, Florida, United States

Ep0215 117

Atlanta, Georgia, United States

...and 61 more locations

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

Clinical Global Impression-Improvement in Participants, Subscale Cognition: Assessment by Parent/Caregiver

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Cognitive function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of cognition was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

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

Clinical Global Impression-Improvement in Participants, Subscale Behavior: Assessment by Parent/Caregiver

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Behavior is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of behavior was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

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

Clinical Global Impression-Improvement in Participants, Subscale Motor Abilities: Assessment by Parent/Caregiver

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Motor abilities function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of motor abilities was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

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

Clinical Global Impression-Improvement in Participants, Subscale Cognition: Assessment by Investigator

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Cognitive function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of cognition was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

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

Clinical Global Impression-Improvement in Participants, Subscale Behavior: Assessment by Investigator

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Behavior is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of behavior was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

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

Clinical Global Impression Improvement in Participants, Subscale Motor Abilities: Assessment by Investigator

The CGI-I scale is used to assess the severity of illness and global improvement in patients. Motor abilities is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of motor abilities was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

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

Number of Participants With Improvement in Seizure Burden as Assessed by the Investigator

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

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