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A Phase 3 Study of Amifampridine Phosphate in Patients With Lambert Eaton Myasthenic Syndrome (LEMS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01377922
Recruitment Status : Completed
First Posted : June 22, 2011
Results First Posted : January 4, 2018
Last Update Posted : January 4, 2018
Information provided by (Responsible Party):
Catalyst Pharmaceuticals, Inc.

Brief Summary:
A Phase 3 study to evaluate the efficacy and safety of Amifampridine Phosphate in patients with Lambert-Eaton Myasthenic Syndrome (LEMS).

Condition or disease Intervention/treatment Phase
Lambert Eaton Myasthenic Syndrome Drug: Amifampridine Phosphate Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Study Start Date : June 2011
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Arm Intervention/treatment
Placebo Comparator: Placebo
Matching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks.
Drug: Placebo
Matching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks.

Experimental: Amifampridine 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.
Drug: Amifampridine 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.
Other Names:
  • 3,4-diaminopyridine phosphate
  • 3,4-DAP phosphate

Primary Outcome Measures :
  1. 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.

  2. 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

Secondary Outcome Measures :
  1. Change From Baseline Timed 25 Foot Walking Test (T25FW) at 14 Days [ Time Frame: Assessment at Baseline and Day 14 ]

    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.

  2. Change in CGI-I Score [ Time Frame: Baseline and Day 14 ]

    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.

    1. = Very much improved
    2. = Much improved
    3. = Minimally improved
    4. = No change
    5. = Minimally worse
    6. = Much worse
    7. = Very much worse

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01377922

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United States, Alabama
Birmingham, Alabama, United States, 35233
United States, Arizona
Scottsdale, Arizona, United States, 85258
United States, California
Los Angeles, California, United States, 90095
Palo Alto, California, United States, 94305
United States, Kansas
Kansas City, Kansas, United States, 66160
United States, New York
New York, New York, United States, 10032
Lyon, France, 69677
Munich, Bavaria, Germany, D-80336
Berlin, Germany, D-10117
Pecs, Hungary, H-7623
Warsaw, Poland, 02 097
Russian Federation
Moscow, Russian Federation, 125367
Belgrade, Serbia, 11000
Madrid, Spain, 28007
Sponsors and Collaborators
Catalyst Pharmaceuticals, Inc.
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Study Director: Charles W Gorodetzky, MD, PhD Chief Medical Officer
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Responsible Party: Catalyst Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01377922    
Other Study ID Numbers: LMS-002
First Posted: June 22, 2011    Key Record Dates
Results First Posted: January 4, 2018
Last Update Posted: January 4, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Lambert-Eaton Myasthenic Syndrome
Pathologic Processes
Myasthenia Gravis
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Paraneoplastic Syndromes
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action