Clinical trial NCT01511978: Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lambert-Eaton Myasthenic Syndrome
Eaton-Lambert Myasthenic Syndrome
Keywords: Lambert-Eaton
Eaton-Lambert
myasthenia
myasthenic
LEMS
LES
DAP
diaminopyridine
3,4-diaminopyridine
3,4-DAP
Lead sponsor: Jacobus Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2012-01-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 or over
2. 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
3. Established diagnosis of LEMS, with documentation provided
4. Continuous use of Jacobus 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 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 \[a patient who remains in bed past this point by choice may still be eligible\]
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, agreed 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. 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

Primary outcomes:
measure: Number of Participants With 30% or More Deterioration in Triple Timed Up & Go (3TUG) Test, Compared to Time-matched Baseline
timeFrame: 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)
Secondary outcomes:
measure: Self-assessment of LEMS-related Weakness, W-SAS
timeFrame: Participants were followed for up to 7 days
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California at Davis
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Jacobus Pharmaceutical
name: Kathy L Aleš, MD
role: STUDY_DIRECTOR
References: