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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Catalyst Pharmaceutical Partners, Inc
Sponsor:
Information provided by (Responsible Party):
Catalyst Pharmaceutical Partners, Inc
ClinicalTrials.gov Identifier:
NCT01377922
First received: June 17, 2011
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Lambert Eaton Myasthenic Syndrome
Drug: Amifampridine Phosphate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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)

Resource links provided by NLM:


Further study details as provided by Catalyst Pharmaceutical Partners, Inc:

Primary Outcome Measures:
  • Change from Baseline Quantitative Myasthenia Gravis (QMG)at 14 days [ Time Frame: Assessment at Baseline, Day 8, and Day 14 ] [ Designated as safety issue: No ]
  • Change in SGI score [ Time Frame: Assessment at Baseline, Days 8 & 14 ] [ Designated as safety issue: No ]
    Subject Global Impression (SGI) is a measure of changes in subject's perception of change in overall wellbeing


Secondary Outcome Measures:
  • Change from Baseline Timed 25 Foot Walking Test (T25FW)at 14 days [ Time Frame: Assessment at Baseline, Day 8, and Day 14 ] [ Designated as safety issue: No ]
  • Change in CGI-I score [ Time Frame: Baseline, Days 8 & 14 ] [ Designated as safety issue: No ]
    Investigator perceived global improvement or change


Estimated Enrollment: 36
Study Start Date: June 2011
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Matching placebo tablets administered 3-4 times a day over 2 weeks.
Drug: Placebo
Matching number of tablets to the individual patient's tablet count of active at baseline.
Experimental: Amifampridine Phosphate
Matching amifampridine phosphate tablets, 10 mg, administered 3-4 times a day for 2 weeks.
Drug: Amifampridine Phosphate
30-80 mg given 3-4 times per day with a maximum single dose of 20 mg (2 x 10 mg tablets).
Other Names:
  • 3,4-diaminopyridine phosphate
  • 3,4-DAP 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01377922

Contacts
Contact: Douglas Winship (305) 529-2522 ext 12 dwinship@catalystpharma.com

  Show 19 Study Locations
Sponsors and Collaborators
Catalyst Pharmaceutical Partners, Inc
Investigators
Study Director: Charles W Gorodetzky, MD, PhD Chief Medical Officer
  More Information

No publications provided

Responsible Party: Catalyst Pharmaceutical Partners, Inc
ClinicalTrials.gov Identifier: NCT01377922     History of Changes
Other Study ID Numbers: LMS-002
Study First Received: June 17, 2011
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lambert-Eaton Myasthenic Syndrome
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
3,4-diaminopyridine
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014