Perampanel Single Ascending Dose Transcranial Magnetic Stimulation Biomarker Study in Amyotrophic Lateral Sclerosis

Study Overview
=================
Brief Summary
-----------------
To evaluate if transcranial magnetic stimulation can be used as a biomarker in Amyotrophic Lateral sclerosis (ALS).

Detailed Description
-----------------
To measure the effect on motor threshold (MT) by transcranial magnetic stimulation (TMS) after a single dose of perampanel at two dose levels.

Official Title
-----------------
Perampanel Single Ascending Dose Transcranial Magnetic Stimulation Biomarker Study in Amyotrophic Lateral Sclerosis

Conditions
-----------------
Amyotrophic Lateral Sclerosis

Intervention / Treatment
-----------------
* Drug: Perampanel
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A probable laboratory supported, probable or definitive ALS diagnosis by revised El Escorial criteria. Sporadic or familial ALS. Ages of 18-70. Agree to use reliable contraception Randomization will occur after a baseline MT has been established; any subject in whom a MT cannot be established will be excluded. Caregiver willing to report adverse behavioral events. - Exclusion Criteria: History of epilepsy. Significant laboratory abnormality (AST or alanine aminotransferase >3x upper limit of normal, or glomerular filtration rate <60) History of aggressive behavior. Subject unwilling to abstain from alcohol for 2 weeks after each dosing. History of drug abuse in the last 5 years Other severe medical conditions, including psychiatric conditions, which would cause an increased risk in the opinion of the investigator, including but not limited to renal failure and liver failure. Skull defect or other physical contraindication for TMS Pacemaker or implanted defibrillator Inability to take study capsule by mouth Females only: Subject is pregnant [as confirmed by a positive serum human chorionic gonadotropin (hCG) test for females of reproductive potential (FRP) only], subject is breastfeeding, or subject is of reproductive potential and does not agree to follow use of reliable contraception. -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a pilot study for the assessment of transcranial magnetic stimulation as a biomarker for ALS and to obtain information to guide a dose selection for future biomarker driven Phase 2 studies of Perampanel in ALS.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>Perampanel 4mg PO x1 | Drug: Perampanel<br>* Oral tablet<br>* Other names: Fycompa;|
| Placebo Comparator: Placebo<br>Receiving placebo | Other: Placebo<br>* Placebo (not drug)<br>|
| Experimental: High dose<br>Perampanel 8 mg PO x1 | Drug: Perampanel<br>* Oral tablet<br>* Other names: Fycompa;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor threshold (MT) | Transcranial Magnetic stimulation motor threshold change from baseline | at 4 hours post dose |