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).

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.

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.