Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome

The objectives of the study are to confirm the safety and to test the efficacy of 3,4-DAP in
the treatment of LEMS-related weakness.

This is a phase 2 randomized double-blind placebo-controlled withdrawal study in subjects
with known clinically active LEMS who have been on a chronic stable dose of compassionate
distribution Jacobus 3,4-DAP provided through FDA-approved individual investigator-held
INDs.

Inclusion Criteria:

1. Age 18 or over

2. Ambulatory while taking 3,4-DAP, i.e. the patient can 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 JPC 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 needs 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, agrees 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. Does 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