Firdapse for Post-BOTOX Vocal Weakness

Amifampridine for the Treatment of Transient Vocal Weakness After OnabotulinumtoxinA Injection for Spasmodic Dysphonia

Botox injections into the thyroarytenoid muscle are a predictable and effective treatment for SD, but typically result in transient symptoms of voice weakness and breathiness during the first 2-3 weeks after injection. Investigators hypothesize that voice weakness and breathiness after Botox treatment can be alleviated using amifampridine.

Study Overview

• Status: Completed
• Conditions: Vocal Weakness(Post-BOTOX Injection)
• Intervention / Treatment: Drug: Amifampridine

Detailed Description

Spasmodic dysphonia (SD) is a dystonia which results in vocal breaks. The mainstay of treatment involves injections using Botox (onabotulinumtoxinA), a neuromuscular blocker which inhibits pre-synaptic release of acetylcholine into the neuromuscular junction. Botox injections into the thyroarytenoid muscle are a predictable and effective treatment for SD, but typically result in transient symptoms of voice weakness and breathiness during the first 2-3 weeks after injection. These symptoms can be present for even longer if Botox is over- dosed.

Investigators hypothesize that these initial, transient symptoms of voice weakness and breathiness after Botox treatment can be alleviated using amifampridine which acts at the neuromuscular junction to increase synaptic presence of the neurotransmitter acetylcholine. In these initial studies, investigators will look at patients who have significant breathiness following an injection.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥18 years of age.
2. Capable of providing informed consent.
3. Confirmed physician diagnosis of spasmodic dysphonia.
4. Receives onabotulinumtoxinA for treatment of their spasmodic dysphonia.
5. Experiences significant breathiness ± 5 days following their injection.
6. If sexually active and of childbearing potential, willing to use an acceptable method of contraception (as noted below) from screening visit until 3 months after the last dose of investigational product.

A.NOTE: No adequate clinical data on exposed pregnancies are available for amifampridine. No nonclinical safety data are available regarding the effects of amifampridine on reproductive function. Amifampridine phosphate should not be used during pregnancy. It is unknown whether amifampridine is excreted in human breast milk. The excretion of amifampridine in milk has not been studied in animals. Amifampridine phosphate should not be used during breastfeeding. Acceptable methods of birth control include:

1. Hormonal contraception (e.g., oral contraceptive, transdermal contraceptive, contraceptive implant, or injectable hormonal contraceptive) for at least 3 months prior to study drug administration, throughout the study, and for 3 months after the last dose of study drug.
2. Double-barrier birth control (e.g., a combination of male condom with either cap, diaphragm, or sponge together with spermicide) starting at the Screening visit, throughout the study, and for at least 4 weeks after the last dose of study drug. NOTE: Use of a male and female condom simultaneously is NOT an acceptable method of double-barrier birth control.
3. Intrauterine contraception/device starting at the Screening visit, throughout the study, and for 3 months after the last dose of study drug.
4. Total abstinence from sexual intercourse (only acceptable if it is the preferred and usual lifestyle of the subject) for at least 1 complete menstrual cycle prior to the Screening visit, throughout the study, and for 3 months after the last dose of study drug.
5. Maintenance of a monogamous relationship with a male partner who has been surgically sterilized by vasectomy.

B. NOTE: Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.

Exclusion Criteria:

1. History of epilepsy and/or on medication/treatment for seizures (such as but not limited to valproic acid, lamotrigine, topiramate, carbamazepine, and phenytoin); or, on certain medications that may lower seizure threshold, such as:

   1. anaesthetic drugs (propofol),
   2. antibiotics (penicillins, cephalosporins, imipenem),
   3. some antidepressants (clomipramine, bupropion, and maprotiline),
   4. antipsychotics (clozapine, chlorpromazine),
   5. bronchodilators (aminophylline, theophylline),
   6. Immunomodifiers (cyclosporine), and
   7. Narcotic analgesics (pethidine, fentanyl).
2. Any SGOT, SGPT that are more than 3x upper limit of normal; and, creatinine that is greater than 2.1
3. Women who are pregnant, expecting to get pregnant, or breastfeeding.
4. Any condition that, in the view of the Principal Investigator, places the subject at risk, or subjects with poor treatment compliance.

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: Treatment Arm; subjects will be given active drug and titrated up in 10mg increments (with max single dose being 30mg) until a change or drug side effect is noticed.	Drug: Amifampridine; 10mg tablet; Other Names: Firdapse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Voice Handicap Index-10	VHI-10 is a scale used to assess the severity of problematic symptoms associated with the voice. It is a series of 10 questions. Each questions is answered using numbers 0-4, with 0 meaning the patient never has a problem with that symptom; and, 4 meaning the patient always has a problem with that symptom.	over 2 months

Collaborators and Investigators

• Sponsor: Augusta University
• Investigators: Principal Investigator: Michael H Rivner, MD, Charbonnier Professor Emeritus of Neurology

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2021
• Primary Completion (Actual): May 27, 2025
• Study Completion (Actual): September 23, 2025

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Spasmodic Dysphonia; BOTOX; Onabotulinumtoxin
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Voice Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Dysphonia; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amines; Aminopyridines; 4-Aminopyridine; Amifampridine
• Other Study ID Numbers: SD-DAP-01

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