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

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).

Study Overview

• Status: Completed
• Conditions: Lambert Eaton Myasthenic Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Amifampridine Phosphate

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 Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69677
• Germany
  • Berlin, Germany, D-10117
  • Bavaria
    • Munich, Bavaria, Germany, D-80336
• Hungary
  • Pecs, Hungary, H-7623
• Poland
  • Warsaw, Poland, 02 097
• Russian Federation
  • Moscow, Russian Federation, 125367
• Serbia
  • Belgrade, Serbia, 11000
• Spain
  • Madrid, Spain, 28007
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
  • Arizona
    • Scottsdale, Arizona, United States, 85258
  • California
    • Los Angeles, California, United States, 90095
    • Palo Alto, California, United States, 94305
  • Kansas
    • Kansas City, Kansas, United States, 66160
  • New York
    • New York, New York, United States, 10032

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Assessment at Baseline and Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Baseline and Day 14

Collaborators and Investigators

• Sponsor: Catalyst Pharmaceuticals, Inc.
• Investigators: Study Director: Charles W Gorodetzky, MD, PhD, Chief Medical Officer

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: June 17, 2011
• First Submitted That Met QC Criteria: June 20, 2011
• First Posted (Estimate): June 22, 2011

Study Record Updates

• Last Update Posted (Actual): January 4, 2018
• Last Update Submitted That Met QC Criteria: January 3, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Disease; Neuromuscular Diseases; Neurodegenerative Diseases; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis; Syndrome; Lambert-Eaton Myasthenic Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Membrane Transport Modulators; Neuromuscular Agents; Potassium Channel Blockers; Amifampridine
• Other Study ID Numbers: LMS-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No