Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome (DAPPER)
|Lambert-Eaton Myasthenic Syndrome Eaton-Lambert Myasthenic Syndrome||Drug: Continuous 3,4-DAP Drug: Taper 3,4-DAP to Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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).Masking: Quadruple (Participant, Care Provider, 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|
- 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.
- 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).
|Study Start Date:||January 2012|
|Study Completion Date:||July 2015|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Continuous 3,4-DAP
Subjects continued taking their usual individualized regimen of 3,4-DAP base, 30 to 100 mg daily divided into at least 3 doses.
Drug: Continuous 3,4-DAP
Subjects were maintained on their usual personal dose and schedule of 3,4-DAP base
Placebo Comparator: Taper 3,4-DAP to Placebo
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
Drug: Taper 3,4-DAP to Placebo
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01511978
|United States, California|
|University of California at Davis|
|Sacramento, California, United States, 95817|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|United States, North Carolina|
|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|
|Study Director:||Kathy L Aleš, MD||Jacobus Pharmaceutical|