Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy

NCT ID: NCT02655198

Last Updated: 2023-09-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2024-12-31

Brief Summary

In this trial, the potential anti-epileptic effect of low dose fenfluramine in Lennox Gastaut epilepsy will be studied. An exploratory dose finding add-on trial is proposed. At baseline and at the end of the study, ECG and ultrasound of the heart will be performed as part of the safety follow up.

Conditions

Epilepsy; Lennox Gastaut Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

fenfluramine

Experimental : one armed open label study :

Add-on fenfluramine in refractory Lennox Gastaut patients. Starting dose 0.2mg/kg/day. In non-responders (<50% seizure frequency decrease), dose will be uptitrated every 4 weeks from 0,2 to 0,4 and max 0,8 mg/kg/day (max 30 mg). Total duration study and max exposure to the drug 20 weeks

Group Type: EXPERIMENTAL

Fenfluramine

Intervention Type: DRUG

study of efficacy and safety of add-on fenfluramine at different dosages in refractory Lennox Gastaut patients : 0.2 - 0.4 and 0.8 mg/kg/day (max 30 mg).

Interventions

Fenfluramine

study of efficacy and safety of add-on fenfluramine at different dosages in refractory Lennox Gastaut patients : 0.2 - 0.4 and 0.8 mg/kg/day (max 30 mg).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Electro-clinical epilepsy syndrome compatible with Lennox Gastaut syndrome:

• Minimum requirements (based on ILAE epilepsydiagnosis.org):

• Multiple seizure types including in any case tonic seizures
• EEG shows slow spike waves and abnormal background
• Abnormal cognitive development
• MRI compatible with Lennox Gastaut epilepsy : no progressive disease
• Drug resistant:

• at least 4 documented seizures in the last 4 weeks before inclusion (minimum 4 seizures in at least 2 separate weeks) Seizure types eligible for inclusion are : generalized tonic-clonic seizures GTC , tonic seizures TS , atonic seizures AS or clearly recognizable focal seizures FS.
• on >= 2 AEDs (including VNS) during the 4 weeks before inclusion (no changes in treatment before inclusion and during the trial)
• Age between 3 and 18 years
• Subject is male or non-pregnant, non-lactating female. Female subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative urine pregnancy test. Subjects of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control, which includes abstinence, while being treated on this study and for 90 days after the last dose of study drug.

Exclusion Criteria

• Known clinical cardiovascular abnormalities (including valvular problems, shunts, pulmonary hypertension, exercise intolerance)
• Any cardiac ultrasound/ECG abnormalities at baseline
• Weight below percentile 3 for age at baseline
• Subject is receiving concomitant therapy with: centrally-acting anorectic agents; monoamine oxidase 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, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates.
• Subject is unwilling to refrain from large or daily servings of grapefruits and/or Seville oranges, and their juices beginning with the Baseline Period and throughout the study.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zogenix, Inc.

INDUSTRY

Sponsor Role: collaborator

KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Lieven Lagae

Professor Paediatric Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lieven G Lagae, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Katolieke Universiteit Leuven, University Hospitals Gasthuisberg

Locations

University Hospitals UZ Leuven

Leuven, , Belgium

Countries

Belgium

References

Lagae L, Schoonjans AS, Gammaitoni AR, Galer BS, Ceulemans B. A pilot, open-label study of the effectiveness and tolerability of low-dose ZX008 (fenfluramine HCl) in Lennox-Gastaut syndrome. Epilepsia. 2018 Oct;59(10):1881-1888. doi: 10.1111/epi.14540. Epub 2018 Aug 26.

Reference Type: DERIVED

PMID: 30146701 (View on PubMed)

Other Identifiers

S58545

Identifier Type: -

Identifier Source: org_study_id