Effect of Amifampridine on Neuromuscular Transmission in Patients Treated With OnabotulinumtoxinA

Study Overview
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Brief Summary
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if amifampridine can improve neuromuscular transmission in muscles previously injected with OnabotulinumtoxinA (BTX-A)

Detailed Description
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Amifampridine may also be effective in treating the sequelae of botulinum toxin injections and this study will determine if neuromuscular transmission as measured by single fiber electromyography is improved in patients treated with BTX-A following administration of amifampridine

Official Title
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A Proof of Concept Study of the Effect of Amifampridine (Firdapse®) on Neuromuscular Transmission in Patients Treated With OnabotulinumtoxinA (Botox®, BTX-A)

Conditions
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Botulism, Iatrogenic Botulism

Intervention / Treatment
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* Drug: Amifampridine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-80 years of either gender and of any racial background Underwent BTX-A injection of facial muscles including frontalis with a total dose between 100-200 units between 80 and 150 days prior to study Have decision-making capacity to provide informed consent to study drug dosing and Single Fiber Electromyography (SFEMG) Exclusion Criteria: History of cardiac arrhythmia History of seizures or uncontrolled asthma History of renal or hepatic disease History of any generalized neuromuscular disease History of Bell's Palsy or facial nerve trauma History of treatment with or sensitivity to amifampridine, 3,4 diaminopyridine (DAP) or 4-aminopyridine (Ampyra®) Currently experiencing sequelae of previous BTX-A treatment Current use of pyridostigmine (known to alter neuromuscular transmission) Use of any investigational drug or device within 30 days of enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: before-after study that will measure neuromuscular jitter before and after administration of amifampridine
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amifampridine will be orally administered to study participants<br>Amifampridine will be orally administered to study participants following completion of the baseline SFEMG. Post-dose SFEMG will commence at 30 minutes following dosing and will be completed within 30 minutes. The participant will remain under observation in the Diagnostic Neurology suite for 2 hours after dosing so it is estimated that the entire protocol including monitoring will be completed within 2-3 hours. | Drug: Amifampridine<br>* a single dose of amifampridine (20mg) will be orally administered<br>* Other names: Firdapse;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of abnormal pairs | Wilcoxon's test for paired data will be used to analyze baseline and post-treatment percent abnormal pairs | Hour 3 | 
| Percentage of Jitter | Wilcoxon's test for paired data will be used to analyze baseline and post-treatment mean jitter | Hour 3 | 
| Percentage of pairs that show blocking | Wilcoxon's test for paired data will be used to analyze baseline and post-treatment percent blocking | Hour 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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botulinum toxin injections, Systemic botulism, neuromuscular transmission, single fiber electromyography, amifampridine