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

Jacobus Pharmaceutical

Status and phase: Completed; Phase 2

Conditions: Eaton-Lambert Myasthenic Syndrome; Lambert-Eaton Myasthenic Syndrome

Treatments: Drug: Continuous 3,4-DAP; Drug: Taper 3,4-DAP to Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01511978

JPC 3,4-DAPPER

Details and patient eligibility

About

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

Full description

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

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

Enrollment: 32 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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32 participants in 2 patient groups, including a placebo group

Continuous 3,4-DAP

Active Comparator group

Description:

Subjects continued taking their usual individualized regimen of 3,4-DAP base, 30 to 100 mg daily divided into at least 3 doses.

Treatment:

Drug: Continuous 3,4-DAP

Taper 3,4-DAP to Placebo

Placebo Comparator group

Description:

Subjects were tapered over 3 days from their usual individualized regimen of 3,4-DAP base (30 to 100 mg daily divided into at least 3 doses) to placebo with up to an additional 16 hours of placebo before resuming their usual pre-study regimen of 3,4-DAP base

Treatment:

Drug: Taper 3,4-DAP to Placebo