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

Lambert-Eaton Myasthenic Syndrome Clinical Trial

— DAPPER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01511978
• Other study ID #: JPC 3,4-DAPPER
• Status: Completed
• Phase: Phase 2
• First received: December 24, 2011
• Last updated: July 7, 2017
• Start date: January 2012
• Est. completion date: July 2015

Study information

• Verified date: July 2017
• Source: Jacobus Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 2015
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Eaton-Lambert Myasthenic Syndrome
• Lambert-Eaton Myasthenic Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Duke University	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Oregon Health & Science University	Portland	Oregon
United States	University of California at Davis	Sacramento	California
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Jacobus Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With 30% or More Deterioration in Triple Timed Up & Go (3TUG) Test, Compared to Time-matched Baseline	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.	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	Self-assessment of LEMS-related Weakness, W-SAS	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).	Participants were followed for up to 7 days