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Lambert Eaton Myasthenic Syndrome

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Patients with clinically-confirmed LEMS will receive 3, 4 DAP by mouth in slowly increasing doses. Treatment will begin with 5 mg three times a day and will increase by 50% every two weeks to 10-15 mg three to six times a day, as clinically needed, and if tolerated.

3, 4 DAP

David Richman, MD

A new drug called 3,4-Diaminopyridine (3,4-DAP) is currently under investigation for treatment of the symptoms of Lambert-Eaton Myasthenic Syndrome (LEMS). This is an expanded access trial, which means that although data from this study will be collected and reported to the US Food and Drug Administration (FDA)and the drug manufacturer, this is not a formal study of drug in LEMS.

If you decide volunteer, you will be evaluated by a neurologist to determine your eligibility to receive 3, 4-DAP by a review of your medical history, medication regimen (the medications you are taking) and a neurological examination. If you are a female of child-bearing potential, a serum pregnancy test will be done to ensure that you are not pregnant. Once it is determined that this treatment is appropriate for your care, you will begin taking 3, 4 DAP by mouth in slowly increasing doses. Treatment will begin with 5mg three times a day, as clinically needed, and if tolerated. You will be monitored for strength and side effects by routine clinic visits at initial intervals of once a month, increasing to intervals of every 12 months as permitted. Blood will be drawn (approximately 1 tablespoon) at every clinic visit or as often as the investigator deems necessary to assess your liver/kidney function and blood counts. You will have an EKG (a test to see how your heart is functioning) at your first study visit, after 6 months of taking 3,4 DAP and again every 2 years. Treatment will be continued indefinitely if a good clinical response is achieved. This study is planned to last indefinitely.

The dosage of 3, 4DAP is individually adjusted. The usual range is 10-15 mg 3-4 times per day for the full effect and will increase by 50% every two weeks to 10-15 mg three to six times a day, as needed and if tolerated. Dosages above the full effect level will not provide an additional benefit and should not be used. 3, 4 DAP is a convulsant (causes seizures). A total of 100 mg/day is the maximum dosage allowed.

Patients with clinically-confirmed LEMS will receive 3, 4-DAP by mouth in slowly increasing doses. Treatment will begin with 5 mg, three times a day and will increase by 50% every two weeks to 10-15 mg, three to six times a day, as clinically needed, and if tolerated. Patients will be monitored for strength and side effects via routine out-patient clinic visits at initial intervals of 1 month, increasing to intervals of 12 months as permitted. Results of treatment and adverse events will be reported to the FDA. Treatment will be continued indefinitely if a good clinical response is achieved and side effects are tolerable.

Treatment of Lambert-Eaton Syndrome With 3,4 DAP

Treatment of Lambert-Eaton Syndrome With 3, 4-Diaminopyridine

Jacobus Pharmaceutical

David P. Richman, MD

Principal Investigator, Professor

Diseases and Abnormalities at or Before Birth

Myasthenic Syndromes, Congenital

Genetic Diseases, Inborn

Congenital Myasthenic Syndromes

The investigator will prescribe an initial dose of 3,4 diaminopyridine (DAP) by mouth based on the participant's weight. This initial dose may be modified later according to the participant's response to treatment.

3,4-Diaminopyridine

Ricardo Maselli, MD

Congenital myasthenia is a potentially lethal disorder, which, even with careful management, significantly impedes participation in normal daily functions. Currently approved therapies have had little impact on promoting a normal quality of life activity in these patients. The goal is to systematically examine the effect of 3,4-DAP on the natural course of this disease and to gain additional experience in titrating 3,4-DAP with other available therapies to maximize clinical function and development in this patient population.

The specific aim of this study is to evaluate the use of 3,4 Diaminopyridine (DAP) on selected patients proven by genetic or serum antibody testing to have Congenital Myasthenic Syndrome (CMS), prescribe 3,4 DAP, and then clinically evaluate the response.

The subject population will consist of selected patients proven by genetic testing, muscle biopsy or antibody testing to have CMS. Consideration for entry in our clinical study will require referral from a treating pediatrician or neurologist. Dr. Maselli will examine patients and deem which are appropriate for neurophysiologic examinations at the University of California, Davis Medical Center. In vitro neuromuscular recordings of anconeus muscle biopsy material (as well as standard light and electron morphologic analysis) or documentation of a genetic mutation associated with congenital myasthenia will be required in some patients to confirm the diagnosis of CMS.

If a participant decides to volunteer, and if the diagnosis of Congenital Myasthenic Syndrome (CMS) has not been established, the participant may need to undergo a muscle biopsy or a blood sampling for DNA testing. The investigators will obtain a blood test (serum chemistry) before participants start treatment and then once a year after the start of 3,4-DAP treatment. Participants will also have an electrocardiograph (EKG) before starting treatment, and every 2 years after the start of 3,4-DAP treatment. All study participants will then return to the clinic once each year (or more often if the neurologist feels it is necessary) for follow-up care.

Participants will receive treatment with the study drug until it is approved by the FDA for use in patients with CMS, until the investigator stops the study drug (because it doesn't work for the participant or it is unsafe for to take), or until the study is ended for other reasons (i.e. safety concerns are discovered, etc.), whichever comes first. Participants will be allowed to stay on other medications for myasthenia or add other medications to treat their condition, as necessary.

If participants have an unclear history of episodes resembling seizures as determined by the investigator, they should not to drive or operate heavy machinery for the first 6 months of the study.

Participants may not participate in this study if they are pregnant or breastfeeding or if they are a woman of childbearing potential who plans to become pregnant while on the study. It is unclear how 3,4 DAP can effect an unborn fetus. Therefore, women of childbearing potential will have a pregnancy test prior to starting the study drug and periodically throughout the study, if needed. Participants who think they may have become pregnant during the study should tell the study doctor immediately.

Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia

Catalyst Pharmaceuticals, Inc.

Ricardo Maselli

Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Treatment of Lambert-Eaton Syndrome With 3,4 DAP	NCT00704925	Lambert Eaton M...	3, 4 DAP	18 Years -	University of California, Davis
Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia	NCT03062631	Congenital Myas...	3,4-Diaminopyri...	3 Months - 75 Years	University of California, Davis

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