Lambert-Eaton Myasthenic SyndromePhase 2DAPPERNCT01511978
Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome
A Phase 2 study testing Continuous 3,4-DAP in people with Lambert-Eaton Myasthenic Syndrome and Eaton-Lambert Myasthenic Syndrome, run by Jacobus Pharmaceutical at 7 sites in United States.
Trial summary
Hypothesis: 3,4-Diaminopyridine base (3,4-DAP) improves Lambert-Eaton Myasthenic Syndrome (LEMS)-related weakness. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lambert-Eaton Myasthenic Syndrome, Eaton-Lambert Myasthenic Syndrome
- What is being tested?
- Continuous 3,4-DAP
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 7 sitesUnited States
- Study dates
- Jan 2012to Jul 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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]
Show all 12Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Duke University
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Oregon Health & Science University
Portland, Oregon, 97239
University of California at Davis
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84132
About this study
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
Hypothesis: 3,4-Diaminopyridine base (3,4-DAP) improves Lambert-Eaton Myasthenic Syndrome (LEMS)-related weakness.
Read the 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.
- Being tested
- Continuous 3,4-DAP, Taper 3,4-DAP to Placebo
- Keywords
- Lambert-Eaton, Eaton-Lambert, myasthenia, myasthenic, LEMS, LES, DAP, diaminopyridine, 3,4-diaminopyridine, 3,4-DAP
- Medical subject headings
- Lambert-Eaton Myasthenic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous 3,4-DAPDrug
Also called 3,4-Diaminopyridine, 3,4-Pyridinediamine, Diamino-3,4-pyridine
Subjects were maintained on their usual personal dose and schedule of 3,4-DAP base
Taper 3,4-DAP to PlaceboDrug
Also called 3,4-Diaminopyridine, 3,4-Pyridinediamine, Diamino-3,4-pyridine, 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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Taper 3,4-DAP to Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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).
Measured: Participants were followed for up to 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionFeb 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lambert-Eaton Myasthenic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jacobus Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kathy L Aleš, MD, Study director, Jacobus Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01511978
- Sponsor's protocol ID
- JPC 3,4-DAPPER
- Acronym
- DAPPER
- Status last verified
- Jul 2017
- First submitted
- 24 Dec 2011
- Last updated
- 11 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01511978
- Acronym / sponsor ID
- DAPPER / JPC 3,4-DAPPER
- Keywords
- Lambert-Eaton, Eaton-Lambert, myasthenia, myasthenic, LEMS, LES, DAP, diaminopyridine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Jacobus PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 19 Jan 2012 (estimated)
- Results
- Posted 11 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Continuous 3,4-DAP | Active comparator | Drug: Continuous 3,4-DAPSubjects continued taking their usual individualized regimen of 3,4-DAP base, 30 to 100 mg daily divided into at least 3 doses. |
| Taper 3,4-DAP to Placebo | Placebo comparator | Drug: Taper 3,4-DAP to PlaceboSubjects 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous 3,4-DAPAlso: 3,4-Diaminopyridine, 3,4-Pyridinediamine, Diamino-3,4-pyridineSubjects were maintained on their usual personal dose and schedule of 3,4-DAP base | Drug | Continuous 3,4-DAP |
| Taper 3,4-DAP to PlaceboAlso: 3,4-Diaminopyridine, 3,4-Pyridinediamine, Diamino-3,4-pyridine, PlaceboSubjects 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 | Drug | Taper 3,4-DAP to Placebo |
Primary outcome
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.
1 secondary outcome
Self-assessment of LEMS-related Weakness, W-SAS
Time frame: Participants were followed for up to 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Lambert-Eaton Myasthenic Syndrome
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Active, not recruitingObservational study
A Natural History Study in Participants With Congenital Myasthenic Syndromes (CMS) Due to Mutations in DOK7, MUSK, AGRN, or LRP4
Congenital Myasthenic Syndrome
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruitingPhase 3
A Study to Assess Efficacy and Safety of Adimanebart in Adult and Pediatric Participants With DOK7-,MUSK-, AGRN-, or LRP4- Congenital Myasthenic Syndromes (CMS)
Congenital Myasthenic Syndrome, CMS
RecruitingPhase 1
Patients With Congenital Myasthenic Syndrome Will be Treated With Umbilical or Placental Derived Mesenchymal Stem Cell Exosome Solution
Congenital Myasthenic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathy L Aleš, MD study director
Jacobus Pharmaceutical
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Continuous 3,4-DAP in people with Lambert-Eaton Myasthenic Syndrome and Eaton-Lambert Myasthenic Syndrome, run by Jacobus Pharmaceutical at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2017.