Safety and Tolerability of Perampanel in Amyotrophic Lateral Sclerosis Patients

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).

Study Overview

• Status: Terminated
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Fycompa

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Lebanon
  • Beirut, Lebanon, 1107 2020
    • Johnny S. Salameh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fycompa; 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; 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.; Other Names: Perampanel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: As measured by change in ALSFRS-R score	Efficacy as measured by change in ALS Functional Rating Scale Revised -ALSFRS-R score ALSFRS-R score is of 12 items with total score of 48(each item score on a scale of 4); 0 reflects severe disability and 48 is the normal score.	During study period up to 4 weeks post- study

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 27, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Tolerability; Perampanel
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: IM.JS.03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No