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

NCT01377922 | Completed Phase 3 Results DMC

• 1 other identifier: LMS-002
• Study Type: interventional
• Target: 38
• Locations: 8 countries
• Sites: 14

Brief Summary

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

Conditions

Lambert Eaton Myasthenic Syndrome

Outcome Measures

Primary Outcomes (2)

• 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. 1. Terrible 2. Mostly dissatisfied 3. Mixed 4. Partially satisfied 5. Mostly satisfied 6. Pleased 7. Delighted

  Assessment at Baseline and Day 14

Secondary Outcomes (2)

• Change From Baseline Timed 25 Foot Walking Test (T25FW) at 14 Days

  Assessment at Baseline and Day 14

• Change in CGI-I Score

  Baseline and Day 14

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Amifampridine Phosphate

EXPERIMENTAL

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

Interventions

Amifampridine Phosphate DRUG

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.

Also known as: 3,4-diaminopyridine phosphate, 3,4-DAP phosphate

Amifampridine Phosphate

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Catalyst Pharmaceuticals, Inc.: lead

Study Sites (14)

Unknown Facility

Birmingham, Alabama, 35233, United States

Location

Unknown Facility

Scottsdale, Arizona, 85258, United States

Location

Unknown Facility

Los Angeles, California, 90095, United States

Location

Unknown Facility

Palo Alto, California, 94305, United States

Location

Unknown Facility

Kansas City, Kansas, 66160, United States

Location

Unknown Facility

New York, New York, 10032, United States

Location

Unknown Facility

Lyon, 69677, France

Location

Unknown Facility

Munich, Bavaria, D-80336, Germany

Location

Unknown Facility

Berlin, D-10117, Germany

Location

Unknown Facility

Pécs, H-7623, Hungary

Location

Unknown Facility

Warsaw, 02 097, Poland

Location

Unknown Facility

Moscow, 125367, Russia

Location

Unknown Facility

Belgrade, 11000, Serbia

Location

Unknown Facility

Madrid, 28007, Spain

Location

MeSH Terms

Conditions

Lambert-Eaton Myasthenic Syndrome

Interventions

Amifampridine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

4-Aminopyridine; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gary Ingenito
• Organization: Catalyst Pharmaceuticals, Inc.

gingenito@catalystpharma.com

305-420-3200

Study Officials

• Charles W Gorodetzky, MD, PhD

  Chief Medical Officer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2011
• First Posted: June 22, 2011
• Study Start: June 1, 2011
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: January 4, 2018
• Results First Posted: January 4, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); SE (1); PL (1); DE (2); US (6); FR (1); RU (1); HU (1)