Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome
Condition: Lambert-Eaton Myasthenic Syndrome; Eaton-Lambert Myasthenic Syndrome
MeSH terms: Lambert-Eaton Myasthenic Syndrome; Syndrome
Intervention: Continuous 3,4-DAP; Taper 3,4-DAP to Placebo
Intervention description: Subjects were maintained on their usual personal dose and schedule of 3,4-DAP base; Subjects were tapered over 3 days from their usual regimen of 3,4-DAP base to placebo with up to an additional 16 hours of placebo before resuming their usual pre-study regimen of 3,4-DAP base
Intervention MeSH terms: Amifampridine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This was a multicenter, randomized, double-blind, placebo-controlled withdrawal study to assess the safety and efficacy of 3,4-DAP in subjects on a stable regimen of all LEMS-related treatments, including 3,4-DAP, for a minimum of 3 months prior to study entry. Subjects who met all study entry criteria were randomized in a 1:1 ratio to continue their current treatment regimen (Group A, continuous 3,4-DAP) or tapered withdrawal from 3,4-DAP (Group B, taper to placebo).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lambert-Eaton; Eaton-Lambert; myasthenia; myasthenic; LEMS; LES; DAP; diaminopyridine; 3,4-diaminopyridine; 3,4-DAP

Summary:

      Hypothesis: 3,4-Diaminopyridine base (3,4-DAP) improves Lambert-Eaton Myasthenic Syndrome
      (LEMS)-related weakness.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18 or over

          2. Ambulatory while taking 3,4-DAP, i.e. the patient was able to perform the timed up and
             go (TUG), either with or without an assistive device

          3. Established diagnosis of LEMS, with documentation provided

          4. Continuous use of Jacobus 3,4-DAP for at least 3 months

          5. Minimum of 3 doses per day with no single dose less than 10 mg of 3,4-DAP

          6. The patient needed to wait about 15 to 30 minutes to experience an unequivocal
             improvement in a LEMS-induced dysfunction after they take their first dose of 3,4-DAP
             in the morning [a patient who remains in bed past this point by choice may still be
             eligible]

          7. Stable regimen of all LEMS-related treatments for at least 3 months

          8. Stable daily regimen of other medications (prescription and over-the-counter) for a
             minimum of 1 month

          9. Willing to chance being tapered off of 3,4-DAP

         10. Fluency in English

         11. If applicable, agreed to use birth control during heterosexual intercourse until at
             least 2 weeks after completion of study

         12. A signed informed consent by the study subject

        Exclusion Criteria:

          1. Last monoclonal antibody treatment (e.g. rituximab) was less than 6 months ago (i.e.,
             recent treatment is an exclusion)

          2. Clinically significant or poorly controlled condition that in the opinion of the study
             personnel might pose an unacceptable risk to the patient if entered into the study

          3. Respiratory failure requiring intubation while on 3,4-DAP with no precipitating event
             or medication

          4. Use of any investigational drug other than 3,4-DAP within the last 30 days

          5. Pregnant or lactating

          6. Current use of other aminopyridines (e.g.4-AP) or guanidine

          7. Did not display a sufficiently large response to 3,4-DAP during the baseline
             observation period in the CRU to detect a decline during withdrawal of 3,4-DAP