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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Jacobus Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01511978
First received: December 24, 2011
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Lambert-Eaton Myasthenic Syndrome
Eaton-Lambert Myasthenic Syndrome
Drug: 3,4-DAP
Drug: 3,4-DAP Taper to Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inpatient Double-Blind Placebo-Controlled Withdrawal Study of 3,4-Diaminopyridine Base (3,4-DAP) in Subjects With Known Lambert-Eaton Myasthenic Syndrome

Resource links provided by NLM:


Further study details as provided by Jacobus Pharmaceutical:

Primary Outcome Measures:
  • Triple Timed Up & Go (TUG) Test [ Time Frame: Participants will be followed for up to 7 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Self-assessment of LEMS-related weakness [ Time Frame: Participants will be followed for up to 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2012
Estimated Study Completion Date: July 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 3,4-DAP
Half of the subjects will be randomized to continue taking their usual regimen of 3,4-DAP
Drug: 3,4-DAP
Subjects will maintain their usual dosage using tablets on their regular personal schedule
Other Names:
  • 3,4-Diaminopyridine
  • 3,4-Pyridinediamine
  • Diamino-3,4-pyridine
Placebo Comparator: 3,4-DAP Taper to Placebo
Half of the subjects will be randomized to gradually taper their dose of 3,4-DAP down to placebo
Drug: 3,4-DAP Taper to Placebo
Subjects will take decreasing amounts of 3,4-DAP using tablets on their regular personal schedule
Other Names:
  • 3,4-Diaminopyridine
  • 3,4-Pyridinediamine
  • Diamino-3,4-pyridine
  • Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01511978

Locations
United States, California
University of California at Davis
Sacramento, California, United States, 95817
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Jacobus Pharmaceutical
Investigators
Study Director: Kathy L Aleš, MD Jacobus Pharmaceutical
  More Information

No publications provided

Responsible Party: Jacobus Pharmaceutical
ClinicalTrials.gov Identifier: NCT01511978     History of Changes
Other Study ID Numbers: JPC 3,4-DAPPER
Study First Received: December 24, 2011
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Jacobus Pharmaceutical:
Lambert-Eaton
Eaton-Lambert
myasthenia
myasthenic
LEMS
LES
DAP
diaminopyridine
3,4-diaminopyridine
3,4-DAP

Additional relevant MeSH terms:
Syndrome
Lambert-Eaton Myasthenic Syndrome
Disease
Pathologic Processes
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Paraneoplastic Syndromes
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 16, 2014