Skip to main content
OpenTrials
Completed

NCT Number: NCT01511978

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

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Lambert-Eaton Myasthenic Syndrome Autoimmune Diseases Autoimmune Diseases of the Nervous System Eaton-Lambert Myasthenic Syndrome Immune System Diseases Myasthenia Gravis Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms Neurodegenerative Diseases Neuromuscular Diseases Neuromuscular Junction Diseases Paraneoplastic Syndromes Paraneoplastic Syndromes, Nervous System

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of California at Davis, Sacramento, California, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 or over
  • 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
  • Established diagnosis of LEMS, with documentation provided
  • Continuous use of Jacobus 3,4-DAP for at least 3 months
  • Minimum of 3 doses per day with no single dose less than 10 mg of 3,4-DAP
  • 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]
  • Stable regimen of all LEMS-related treatments for at least 3 months
  • Stable daily regimen of other medications (prescription and over-the-counter) for a minimum of 1 month
  • Willing to chance being tapered off of 3,4-DAP
  • Fluency in English
  • If applicable, agreed to use birth control during heterosexual intercourse until at least 2 weeks after completion of study
  • A signed informed consent by the study subject

Exclusion criteria

  • Last monoclonal antibody treatment (e.g. rituximab) was less than 6 months ago (i.e., recent treatment is an exclusion)
  • 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
  • Respiratory failure requiring intubation while on 3,4-DAP with no precipitating event or medication
  • Use of any investigational drug other than 3,4-DAP within the last 30 days
  • Pregnant or lactating
  • Current use of other aminopyridines (e.g.4-AP) or guanidine
  • 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

Treatment and study plan

Continuous 3,4-DAP

Drug

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

Other names: 3,4-Diaminopyridine, 3,4-Pyridinediamine, Diamino-3,4-pyridine

Taper 3,4-DAP to Placebo

Drug

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

Other names: 3,4-Diaminopyridine, 3,4-Pyridinediamine, Diamino-3,4-pyridine, Placebo

Primary outcomes

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

    Time frame: Baseline period (days 0, 1, 2); Randomized treatment period (starting with last dose of day 2, and days 3, 4, 5, and ending with first dose on day 6 when pre-randomization regimen was resumed, or rescue, if indicated sooner)

    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.

Secondary outcomes

  1. Self-assessment of LEMS-related Weakness, W-SAS

    Time frame: Participants were followed for up to 7 days

    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).

Sponsors and collaborators

Lead sponsor

Jacobus Pharmaceutical

Industry

Registry information

Official study title

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

Acronym: DAPPER

Important dates

Study start
2012
Primary completion
2014
Study completion
2015
First posted
Jan 19, 2012
Registry last updated
Jul 11, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.