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

Phase 3

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Amifampridine Phosphate	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.
Placebo	Placebo	Matching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days	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	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

Name	Time	Method
Change From Baseline Timed 25 Foot Walking Test (T25FW) at 14 Days	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.
Change in CGI-I Score	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