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Lambert-Eaton Myasthenic Syndrome

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Lambert Eaton Myasthenic Syndrome

Channel Blockers

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Amifampridine

Potassium Channel Blockers

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

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

Subjects were maintained on their usual personal dose and schedule of 3,4-DAP base

Continuous 3,4-DAP

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

Taper 3,4-DAP to Placebo

Kathy L Aleš, MD

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

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.

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).

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

Inpatient Double-Blind Placebo-Controlled Withdrawal Study of 3,4-Diaminopyridine Base (3,4-DAP) in Subjects With Known Lambert-Eaton Myasthenic Syndrome

The 3TUG time obtained 2 hours after the last dose of the withdrawal period (i.e., at time of theoretical "peak drug effect") was compared to the average time-matched 3TUG tests performed during 2 days of baseline observation prior to randomization.

The study endpoint was a change of more than 30% in the final post-dose 3TUG during the withdrawal period and was based on blinded readings of video recordings of 3TUG tests.

The last post-dose self-assessment of LEMS-related weakness from the withdrawal period with categories of much much weaker (-3), much weaker (-2), somewhat weaker (-1), about the same (0), somewhat stronger (1), much stronger (2), and much much stronger (3).

Jacobus Pharmaceutical

The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events

Subjects were administered their usual dosage on their regular personalized schedule

Continuous 3,4-Diaminopyridine (3,4-DAP)

Subjects were administered decreasing amounts of 3,4-DAP on their regular personalized schedule

3,4-DAP Taper to Placebo

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Height

Weight

Body Mass Index (BMI)

Age at diagnosis

Time between symptom onset and diagnosis

Duration of diagnosis prior to randomization

Positive P/Q type voltage-gated calcium channel (VGCC) antibodies at screening

Compound Muscle Action Potential (CMAP) consistent with Lambert-Eaton Myasthenia (LEM) at screening

Total Daily Dose of 3,4-DAP at randomization

Number of 3,4-DAP individual daily doses at randomization

Dr. Kathy Aleš, Medical Director

Subjects were continued on their usual pre-randomization 3,4-DAP dosing regimen.

Subjects were tapered off of their pre-randomization 3,4-DAP dosing regimen over 3 days with up to an additional 16 hours of placebo.

Number of Participants With 30% or More Deterioration in Triple Timed Up & Go (3TUG) Test, Compared to Time-matched Baseline

Subjects were administered their usual dosage on their regular personalized schedule.

Spots Global Cancer Trial Database for Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome

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