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

NCT01511978 | Completed Phase 2 Results FDA Drug

• 1 other identifier: JPC 3,4-DAPPER
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 7

Brief Summary

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Self-assessment of LEMS-related Weakness, W-SAS

  Participants were followed for up to 7 days

Study Arms (2)

Continuous 3,4-DAP

ACTIVE COMPARATOR

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

Taper 3,4-DAP to Placebo

PLACEBO COMPARATOR

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

Interventions

Continuous 3,4-DAP DRUG

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

Also known as: 3,4-Diaminopyridine, 3,4-Pyridinediamine, Diamino-3,4-pyridine

Continuous 3,4-DAP

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

Also known as: 3,4-Diaminopyridine, 3,4-Pyridinediamine, Diamino-3,4-pyridine, Placebo

Taper 3,4-DAP to Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jacobus Pharmaceutical: lead

Study Sites (7)

University of California at Davis

Sacramento, California, 95817, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Lambert-Eaton Myasthenic Syndrome

Interventions

Amifampridine

Condition Hierarchy (Ancestors)

Myasthenia Gravis; 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

Intervention Hierarchy (Ancestors)

4-Aminopyridine; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Kathy Aleš, Medical Director
• Organization: Jacobus Pharmaceutical Company, Inc.

kathy.ales@jacobus-pharmaceutical.com

6099217447

Study Officials

• Kathy L Aleš, MD

  Jacobus Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: December 24, 2011
• First Posted: January 19, 2012
• Study Start: January 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: July 1, 2015
• Last Updated: July 11, 2017
• Results First Posted: July 11, 2017

Record last verified: 2017-07

Locations

US (7)