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

• ClinicalTrials.gov Identifier: NCT01377922
• Recruitment Status: Completed
• First Posted: June 22, 2011
• Results First Posted: January 4, 2018
• Last Update Posted: January 4, 2018
• Sponsor: Catalyst Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Catalyst Pharmaceuticals, Inc.

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

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

France

Lyon, France, 69677

Germany

Munich, Bavaria, Germany, D-80336

Berlin, Germany, D-10117

Hungary

Pecs, Hungary, H-7623

Poland

Warsaw, Poland, 02 097

Russian Federation

Moscow, Russian Federation, 125367

Serbia

Belgrade, Serbia, 11000

Spain

Madrid, Spain, 28007

Sponsors and Collaborators

Catalyst Pharmaceuticals, Inc.

Investigators

• Study Director: Charles W Gorodetzky, MD, PhD; Chief Medical Officer

More Information

• Responsible Party: Catalyst Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01377922
• Other Study ID Numbers: LMS-002
• First Posted: June 22, 2011
• 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:

Lambert-Eaton Myasthenic Syndrome; Syndrome; Disease; Pathologic Processes; 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; Amifampridine; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Potassium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action