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

Phase 3
Completed
Conditions
Lennox Gastaut Syndrome
Interventions
Drug: Matching Placebo
Drug: ZX008 0.2 or 0.8 mg/kg/day
Registration Number
NCT03355209
Lead Sponsor
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
296
Inclusion Criteria
  • Male or non-pregnant, non-lactating female, age 2 to 35 years, inclusive as of the day of the Screening Visit.
  • Clinical diagnosis of Lennox-Gastaut syndrome, where seizures that result in drops are not completely controlled by current antiepileptic treatments.
  • Onset of seizures at 11 years of age or younger.
  • Abnormal cognitive development.
  • Must be receiving at least 1 concomitant AED and up to 4 concomitant anti-epileptic treatments.

Key

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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Matching PlaceboMatching PlaceboPart 1: Matching ZX008 placebo is supplied as an oral solution.
ZX008 0.2 or 0.8 mg/kg/dayZX008 0.2 or 0.8 mg/kg/dayPart 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.
Open-LabelZX008 0.2 or 0.8 mg/kg/dayPart 2: ZX008 is supplied as an oral solution. Study medication will be administered twice a day (BID) in equally divided doses.
Primary Outcome Measures
NameTimeMethod
Part 1: Change from baseline in frequency of seizures that result in drops in subjects receiving ZX008 compared to placeboUp to 20 weeks maintenance and taper period (T+M)

Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity

Secondary Outcome Measures
NameTimeMethod
Part 2: Adverse events and related safety parameters in subjects receiving ZX008 compared to placeboUp to 12 months open label

Safety and tolerability evaluated by reported adverse events, laboratory parameters, physical and neurological examination, vital signs, electrocardiograms, echocardiograms, and body weight

Trial Locations

Locations (72)

Ep0214 144

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Los Angeles, California, United States

Ep0214 117

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Atlanta, Georgia, United States

Ep0214 115

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Gulf Breeze, Florida, United States

Ep0214 105

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Hackensack, New Jersey, United States

Ep0214 146

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Dallas, Texas, United States

Ep0214 301

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Heidelberg, Australia

Ep0214 802

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Brussels, Belgium

Ep0214 908

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Kiel, Germany

Ep0214 901

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Vogtareuth, Germany

Ep0214 110

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Chicago, Illinois, United States

Ep0214 145

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San Antonio, Texas, United States

Ep0214 106

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Salt Lake City, Utah, United States

Ep0214 1005

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Lille Cedex, France

Ep0214 101

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San Francisco, California, United States

Ep0214 149

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Washington, District of Columbia, United States

Ep0214 104

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Miami, Florida, United States

Ep0214 121

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Orlando, Florida, United States

Ep0214 140

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Bethesda, Maryland, United States

Ep0214 112

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Boston, Massachusetts, United States

Ep0214 136

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Grand Rapids, Michigan, United States

Ep0214 132

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Saint Paul, Minnesota, United States

Ep0214 142

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New York, New York, United States

Ep0214 131

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Cleveland, Ohio, United States

Ep0214 126

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Fort Worth, Texas, United States

Ep0214 139

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York, Pennsylvania, United States

Ep0214 125

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Tacoma, Washington, United States

Ep0214 803

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Bruxelles, Belgium

Ep0214 302

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South Brisbane, Australia

Ep0214 204

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Toronto, Canada

Ep0214 201

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Vancouver, Canada

Ep0214 701

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Dianalund, Denmark

Ep0214 1004

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Bordeaux Cedex, France

Ep0214 1006

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Bron, France

Ep0214 1007

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Marseilles, France

Ep0214 906

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Freiburg, Germany

Ep0214 1001

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Paris, France

Ep0214 1002

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Paris, France

Ep0214 902

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Bielefeld, Germany

Ep0214 903

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Radeberg, Germany

Ep0214 905

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Jena, Germany

Ep0214 1211

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Bologna, Italy

Ep0214 1204

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Genova, Italy

Ep0214 1201

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Firenze, Italy

Ep0214 1206

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Roma, Italy

Ep0214 1208

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Roma, Italy

Ep0214 1507

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Osaka, Japan

Ep0214 1504

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Omura, Japan

Ep0214 1501

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Okayama, Japan

Ep0214 1508

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Sapporo-city, Japan

Ep0214 1502

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Shizuoka, Japan

Ep0214 1401

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Zwolle, Netherlands

Ep0214 1604

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Guadalajara, Mexico

Ep0214 1702

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Bydgoszcz, Poland

Ep0214 1701

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Krakow, Poland

Ep0214 1105

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Barcelona, Spain

Ep0214 1101

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Mirasierra, Spain

Ep0214 1107

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Barcelona, Spain

Ep0214 502

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Göteborg, Sweden

Ep0214 1102

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Pamplona, Spain

Ep0214 150

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Hartsdale, New York, United States

Ep0214 147

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Royal Oak, Michigan, United States

Ep0214 120

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Philadelphia, Pennsylvania, United States

Ep0214 103

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Aurora, Colorado, United States

Ep0214 109

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Rochester, Minnesota, United States

Ep0214 143

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Portland, Oregon, United States

Ep0214 141

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Orlando, Florida, United States

Ep0214 801

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Edegem, Belgium

Ep0214 118

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Livingston, New Jersey, United States

Ep0214 107

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Tucson, Arizona, United States

Ep0214 1510

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Fukuoka, Japan

Ep0214 1506

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Shinjuku-ku, Japan

Ep0214 1505

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Niigata-city, Japan

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