LEMS: Jacobus Expands Trial of 3,4-DAP

Jacobus Pharmaceutical of Princeton, N.J., is continuing its placebo-controlled trial of 3,4-diaminopyridine (3,4-DAP) for people with Lambert-Eaton myasthenic syndrome (LEMS) who have been receiving the drug through Jacbobus' "expanded access" (also called "compassionate use") program. The study, which began in January 2012, was originally by invitation only. It now has expanded to include additional participants.

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

LEMS is caused by a misdirected attack of the immune system on nerve endings at the neuromuscular junction, the place where nerve and muscle fibers connect. The disorder causes muscle weakness and sometimes other symptoms, such as dry mouth or constipation.

In the United States, the disease is treated with medications that suppress the immune system and/or medications that slow the breakdown of acetylcholine (cholinesterase inhibitors).

3,4-DAP increases the release of acetylcholine, a chemical messenger that carries signals from nerve cells to muscle fibers.

Expanded 3,4-DAP trial

In this expanded phase 2 trial, participants will be randomly assigned to continue their usual dosage of 3,4-DAP or to gradually reduce (taper) their 3,4-DAP down to zero (a placebo). Neither the investigators nor the participants will know who is taking their usual dose and who is in the "taper to placebo" group until the trial has been completed.

Study sites are in Sacramento, Calif.; Indianapolis; Durham, N.C.; Portland, Ore.; Nashville, Tenn.; Houston; and Salt Lake City.

Each participant will be screened and then, if considered eligible for the trial, asked to spend up to a week in a clinical research center.

Participants will take "timed up and go" functional tests, which measure how long it takes for someone to move from a sitting to a standing position and then walk a short distance; they also will report their own assessment of LEMS-related weakness.

Participants must:

  • be at least 18 years old;
  • be ambulatory (able to walk) while taking 3,4-DAP (i.e., can perform the timed up and go test, either with or without an assistive device);
  • have an established diagnosis of LEMS, with documentation provided;
  • have been taking Jacobus' 3,4-DAP for at least three months;
  • have been taking a minimum of three doses of 3,4-DAP per day, with no single dose being less than 10 milligrams;
  • see functional improvement after waiting about 15 to 30 minutes after taking the first dose of 3,4-DAP in the morning;
  • have been on a stable regimen of all LEMS-related treatments for at least three months;
  • have been on a stable daily regimen of other medications (prescription and over-the-counter) for a minimum of one month;
  • be willing to chance being tapered off 3,4-DAP;
  • be fluent in English;
  • agree to use birth control until at least two weeks after completion of the study; and
  • sign an informed consent.

Participants must not:

  • have taken a monoclonal antibody drug (such as rituximab) within the previous six months;
  • have a clinically significant or poorly controlled condition that, in the opinion of the study personnel, might pose an unacceptable risk to the patient if he or she enters the study;
  • have experienced respiratory failure requiring intubation while on 3,4-DAP in the absence of a precipitating event or medication;
  • have used any investigational drug other than 3,4-DAP within the last 30 days;
  • be pregnant or lactating (breast-feeding);
  • be taking other aminopyridines (such as 4-AP) or guanidine; or
  • have an insufficient response to 3,4-DAP during the baseline observation period.

To participate

Contact Kathy Ales, M.D., at Jacobus Pharmaceutical, at (609) 921-7447, ext. 238, or kathy.ales@jacobus-pharmaceutical.com; or contact the study site nearest you.

For details, including contact information for each site, see Effectiveness of 3,4-Diaminpyridine in Lambert-Eaton Myasthenic Syndrome (DAPPER); or go to ClinicalTrials.gov and enter NCT01511978 in the search box.

About Clinical Trials

About Clinical Trials

A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur.

MDA has no ability to influence who is chosen to participate in a clinical trial.

To learn more about clinical trials, see Being a Co-Adventurer. For a more refined list of ALS clinical trials, visit
ClinicalTrials.gov, a registry of federally and privately supported clinical trials in the United States and around the world. Select the "Find Studies" tab, and follow the instructions to narrow down your search results.

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