Lambert Eaton Myasthenic SyndromePhase 3NCT01377922
A Phase 3 Study of Amifampridine Phosphate in Patients With Lambert Eaton Myasthenic Syndrome (LEMS)
A Phase 3 study testing Amifampridine Phosphate in people with Lambert Eaton Myasthenic Syndrome, run by Catalyst Pharmaceuticals, Inc. at 14 sites in 8 countries.
Trial summary
A Phase 3 study to evaluate the efficacy and safety of Amifampridine Phosphate in patients with Lambert-Eaton Myasthenic Syndrome (LEMS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lambert Eaton Myasthenic Syndrome
- What is being tested?
- Amifampridine Phosphate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 14 sitesin 8 countries
- Study dates
- Jun 2011to Jul 2016
- Phase
- Phase 3
- 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
Inclusion Criteria: Individuals eligible to participate in this study must meet all of the following inclusion criteria:
- ≥18 years of age
- Confirmed diagnosis of LEMS
- Normal respiratory function
- Normal swallowing function
- If receiving peripherally acting cholinesterase inhibitors a stable dose is required for at least 7 days prior to Screening.
- If receiving oral immunosuppressants a stable dose is required for at least 90 days prior to Screening.
- Negative pregnancy test for females of childbearing potential
- If sexually active, willing to use 2 acceptable methods of contraception
- Willing to perform all study procedures as physically possible.
- Willing and able to provide written informed consent after the nature of the study has been explained and prior to the start of any research-related procedures.
Exclusion Criteria: Individuals who meet any of the following exclusion criteria are not eligible to participate in the study:
- History of epilepsy or seizure.
- Known active brain metastasis.
- Use of Fampridine (4-aminopyridine), and any form of 3,4-diaminopyridine other than the IP provided, such as amifampridine base or Firdapse, during the study.
- Use of medications known to lower the epileptic threshold within 7 days or 5 half-lives.
- Use of medications which inhibit neuromuscular junction function within 7 days or 5 half-lives.
- Use of IVIG, plasmapheresis (plasma exchange), or immunoadsorption within 90 days
- Use of guanidine hydrochloride within 7 days
- Use of rituximab within 12 months
- History of drug allergy to any pyridine-containing substances or any amifampridine phosphate excipient(s).
- Use of any other investigational productwithin 30 days
- Treatment with a concomitant medication that prolongs the QT/QTc interval within 7 days or 5 half-lives.
- Treatment with sultopride (4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-2-methoxybenzamide) within 7 days.
- An abnormal electrocardiogram (ECG).
- Documented history of arrhythmias.
- History of additional risk factors for torsade de pointes.
- Breastfeeding or pregnant or planning to become pregnant (self or partner) at any time during the study.
- Likely or expected to require treatment for cancer within 3 months (90 days) after entering.
- History of severe renal impairment or evidence of severe renal impairment
- Any condition that places the patient at high risk of poor treatment compliance or of not completing the study.
- History of uncontrolled asthma.
Trial locations and contacts
14 sites in 8 countries.
14 sites in 8 countries
United States6 sites
Study site
Birmingham, Alabama, 35233
Study site
Kansas City, Kansas, 66160
Study site
Los Angeles, California, 90095
Study site
New York, New York, 10032
Study site
Palo Alto, California, 94305
Study site
Scottsdale, Arizona, 85258
About this study
Official title: A Phase 3, Double-blind, Placebo-controlled, Randomized Discontinuation Study Followed by Open-label Extension Evaluating Efficacy and Safety of Amifampridine Phosphate in Patients With Lambert-Eaton Myasthenic Syndrome (LEMS)
A Phase 3 study to evaluate the efficacy and safety of Amifampridine Phosphate in patients with Lambert-Eaton Myasthenic Syndrome (LEMS).
Read the detailed description
This multicenter, double-blind, placebo-controlled, randomized (1:1) discontinuation study is a 4-part study designed to evaluate the efficacy and safety of multiple dose administration of amifampridine phosphate in patients with LEMS. Data from parts 2 and 3 (the double-blind parts of the study) are presented in this record.
- Conditions
- Lambert Eaton Myasthenic Syndrome
- Being tested
- Amifampridine Phosphate, Placebo
- 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.
Amifampridine PhosphateDrug
Also called 3,4-diaminopyridine phosphate, 3,4-DAP phosphate
Amifampridine, 30-80 mg given 3-4 times per day with a maximum single dose of 20 mg (2 x 10 mg tablets), for 2 weeks.
PlaceboDrug
Matching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks. Receives: Drug: Placebo |
| Amifampridine Phosphate | Experimental | Amifampridine, 30-80 mg given 3-4 times per day with a maximum single dose of 20 mg (2 x 10 mg tablets), for 2 weeks. Receives: Drug: Amifampridine Phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days
The QMG is a physician-rated test including 13 assessments, including facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each of the 13 items is scored from 0 (none) to 3 (severe). The total score can range from 0 to 39. Increased QMG total score correlates to worsening symptoms of LEMS.
Measured: Assessment at Baseline and Day 14
Change in SGI Score
Subject Global Impression (SGI) is a measure of changes in subject's perception of change in overall wellbeing.
The patient is asked to use the 7-point scale below to rate their impression of the effects of the study medication during the preceding 3 days on their physical well being.
- Terrible
- Mostly dissatisfied
- Mixed
- Partially satisfied
- Mostly satisfied
- Pleased
- Delighted
Measured: Assessment at Baseline and Day 14
Secondary outcomes (2)
Change From Baseline Timed 25 Foot Walking Test (T25FW) at 14 Days
The T25FW test, a component of the Multiple Sclerosis Functional Composite, was a quantitative mobility and leg function performance test based on a timed 25-foot walk (National Multiple Sclerosis Society). The patient was directed to walk a clearly marked 25-foot course as quickly and safely as possible. Following a rest of at least 5 minutes, the timed 25-foot walk was repeated. Patients could use assistive devices, such as canes, crutches, or walkers.
All data were normalized to the number of feet per minute, so if the patient walked 25 feet in less than a minute, the result was a speed greater than 25 feet/minute.
The measurement for the T25FW test was the average speed, expressed in feet/minute, of the 2 completed walks.
Measured: Assessment at Baseline and Day 14
Change in CGI-I Score
The Investigator completed the 7-point CGI I, based on changes in symptoms, behavior, and functional abilities, at the protocol-specified time points compared to the patient's condition at Day 0.
- = Very much improved
- = Much improved
- = Minimally improved
- = No change
- = Minimally worse
- = Much worse
- = Very much worse
Measured: Baseline and Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionJul 2016
- Study completionJul 2016
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catalyst Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Charles W Gorodetzky, MD, PhD, Study director, Chief Medical Officer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01377922
- Sponsor's protocol ID
- LMS-002
- Status last verified
- Jan 2018
- First submitted
- 17 Jun 2011
- Last updated
- 4 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-blind, Placebo-controlled, Randomized Discontinuation Study Followed by Open-label Extension Evaluating Efficacy and Safety of Amifampridine Phosphate in Patients With Lambert-Eaton Myasthenic Syndrome (LEMS)
- ClinicalTrials.gov ID
- NCT01377922
- Acronym / sponsor ID
- LMS-002
- Conditions
- Lambert Eaton Myasthenic Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Catalyst Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 22 Jun 2011 (estimated)
- Results
- Posted 4 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 3 study to evaluate the efficacy and safety of Amifampridine Phosphate in patients with Lambert-Eaton Myasthenic Syndrome (LEMS).
Detailed description
This multicenter, double-blind, placebo-controlled, randomized (1:1) discontinuation study is a 4-part study designed to evaluate the efficacy and safety of multiple dose administration of amifampridine phosphate in patients with LEMS. Data from parts 2 and 3 (the double-blind parts of the study) are presented in this record.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks. |
| Amifampridine Phosphate | Experimental | Drug: Amifampridine PhosphateAmifampridine, 30-80 mg given 3-4 times per day with a maximum single dose of 20 mg (2 x 10 mg tablets), for 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Amifampridine PhosphateAlso: 3,4-diaminopyridine phosphate, 3,4-DAP phosphateAmifampridine, 30-80 mg given 3-4 times per day with a maximum single dose of 20 mg (2 x 10 mg tablets), for 2 weeks. | Drug | Amifampridine Phosphate |
| PlaceboMatching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks. | Drug | Placebo |
Primary outcome
Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days
Time frame: Assessment at Baseline and Day 14
The QMG is a physician-rated test including 13 assessments, including facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each of the 13 items is scored from 0 (none) to 3 (severe). The total score can range from 0 to 39. Increased QMG total score correlates to worsening symptoms of LEMS.
Change in SGI Score
Time frame: Assessment at Baseline and Day 14
Subject Global Impression (SGI) is a measure of changes in subject's perception of change in overall wellbeing. The patient is asked to use the 7-point scale below to rate their impression of the effects of the study medication during the preceding 3 days on their physical well being. 1. Terrible 2. Mostly dissatisfied 3. Mixed 4. Partially satisfied 5. Mostly satisfied 6. Pleased 7. Delighted
2 secondary outcomes
Change From Baseline Timed 25 Foot Walking Test (T25FW) at 14 Days
Time frame: Assessment at Baseline and Day 14
Change in CGI-I Score
Time frame: Baseline and Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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.
Charles W Gorodetzky, MD, PhD study director
Chief Medical Officer
14 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Amifampridine Phosphate in people with Lambert Eaton Myasthenic Syndrome, run by Catalyst Pharmaceuticals, Inc. at 14 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 4 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Germany, France, Hungary, Poland and 3 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 4 Jan 2018). 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?
Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days (time frame: Assessment at Baseline and Day 14). The study lists 2 primary outcomes in all. 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 4 Jan 2018.