Safety and Tolerability of Perampanel in Amyotrophic Lateral Sclerosis Patients

NCT03377309 | Terminated Phase 2

• 1 other identifier: IM.JS.03
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is a fatal progressive neurodegenerative disease affecting motor cortex, brainstem and spinal cord leading to motor neuron death. It is a devastating disease of the anterior and lateral corticospinal tracts with approximately 3 years mean duration from symptoms onset to death, one-fifth survival at 5 years and only 10% may make it to 10 years. Among the neuronal death pathways, excitotoxicity mechanism is considered to be the foremost-involved mechanism. AMPA receptors are thought to be the prime mediator of the fast excitation in spinal motor neurons, where they are expressed ubiquitously. AMPA receptor antagonist was able to prevent this acute degeneration in previous animal studies. The investigators aim to study the tolerability and safety of the novel AMPA antagonist, perampanel, in patients diagnosed with ALS. Perampanel \[2-(2-oxo-1-phenyl-5- pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile\] with its selective non-competitive AMPA antagonism, was recently approved for epilepsy. Various long-term trials studying perampanel in epilepsy showed favorable tolerability profile and most common side effects were mainly: dizziness, headache and somnolence. All patients presenting to Neurology clinics at AUBMC diagnosed with Amyotrophic Lateral Sclerosis, will be considered for the study. Investigators will obtain informed consents from all patients who agree to be enrolled in this study in accordance with institutional review board (IRB) requirements. Patients of both genders and over 18 years old who meet the El Escorial criteria for possible, probable or definite ALS and fit the inclusion criteria will be recruited. Subjects should not be started on riluzole for the past 30 days or stable on a dose of riluzole for at least 30 days prior to the screening process. In titration phase, perampanel dose will be increase by 2mg/day increments every one week to reach a maximum dose of 8 mg/day; reaching the maximum dose in four weeks. Treatment phase will be followed by washout period during which, dose will be tapered by 2mg/day every 5 days (over total of 15 days).

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Safety; Tolerability; Perampanel

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability: Incidence and severity of drug-related adverse effects

  Incidence and severity of drug-related adverse effects

  During study period up to 4 weeks post- study

Secondary Outcomes (1)

• Efficacy: As measured by change in ALSFRS-R score

  During study period up to 4 weeks post- study

Study Arms (1)

Fycompa

EXPERIMENTAL

Dose will be increased by 2mg/day increments every one week to reach a maximum dose of 8 mg/day. Treatment phase will be stable dose for 12 weeks then followed by washout period over 2 weeks.

Drug: Fycompa

Interventions

Fycompa DRUG

Dose will be increased by 2mg/day increments every one week to reach a maximum dose of 8 mg/day. Treatment phase will be stable dose for 12 weeks then followed by washout period over 2 weeks.

Also known as: Perampanel

Fycompa

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Amyotrophic Lateral Sclerosis (ALS) volunteers must be diagnosed within the 3 years prior to participation as having possible, probable, or definite ALS, either sporadic or familial according to modified El Escorial criteria
• Age 18-80, able to provide informed consent, and comply with study procedures
• Participants must not have started riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days, prior to screening (riluzole-naïve participants are permitted in the study)
• Slow VC test equal to or greater than 50% of the predicted value

You may not qualify if:

• The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the participant to provide informed consent
• Exposure to any experimental agent within 30 days of entry or at any time during the trial or enrollment in another research study within 30 days of or during this trial
• Women who are breastfeeding, who are pregnant or are planning to become pregnant
• Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal
• Hepatic insufficiency or abnormal liver function (AST and/or ALT greater than 3 times the upper limit of the normal range)
• Slow VC test less than 50% of the predicted value
• ECG finding of QTc prolongation \> 450 ms
• Patients who had already undergone tracheostomy

Sponsors & Collaborators

• American University of Beirut Medical Center: lead

Study Sites (1)

Johnny S. Salameh

Beirut, 1107 2020, Lebanon

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

perampanel

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Johnny Salameh, MD

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 14, 2017
• First Posted: December 19, 2017
• Study Start: December 1, 2019
• Primary Completion: June 1, 2020
• Study Completion: July 1, 2021
• Last Updated: September 1, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)