Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Immune System Diseases

Rare Diseases

Syndrome

Lambert-Eaton Myasthenic Syndrome

Myasthenia Gravis

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Lambert Eaton Myasthenic Syndrome

Channel Blockers

All Drugs and Chemicals

Amifampridine

Potassium Channel Blockers

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

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.

Amifampridine Phosphate

Placebo

Charles W Gorodetzky, MD, PhD

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.

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)

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.

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

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.

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

Catalyst Pharmaceuticals, Inc.

For this study, the following additional events were considered SAEs:

* A generalized tonic-clonic convulsion/seizure;
* A normal liver function test for a patient at Screening, but the patient developed the following constellation of findings:

  * ALT or AST \>3 times the ULN;
  * total bilirubin \>2 times the ULN; and
  * no other explanation, such as concurrent liver disease or treatment with a potentially hepatotoxic concurrent medication, was found.

Matching placebo tablets, administered 3-4 times a day for 2 weeks.

Placebo tablets indistinguishable from amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.

Part 2 and Part 3 Placebo

Matching amifampridine phosphate tablets, 10 mg, administered 3-4 times a day for 2 weeks.

Amifampridine Phosphate: 30-80 mg given 3-4 times per day with a maximum single dose of 20 mg (2 x 10 mg tablets).

Part 2 and Part 3 Amifampridine Phosphate

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Was the patient taking amifampridine (base or phosphate) immediately prior to enrollment?

Data only for those subjects (7 in the placebo group, 3 in the amifampridine group) who were taking amifampridine prior to enrollment.

If yes, number of continuous days of amifampridine exposure immediately prior to enrollment

Gary Ingenito

Baseline

Day 14

Change from Baseline

Matching placebo tablets administered 3-4 times a day over 2 weeks.

Placebo: Matching number of tablets to the individual patient's tablet count of active at baseline.

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

Estimated via a MMRM with change from baseline (Day 1, Part 2), Day 8, and Day 14 as the dependent variable and terms for treatment, time (Day 8, Day 14), treatment-by-time interaction, and double-blind baseline SGI score as fixed effects and patient as a random effect. The model assumed time effect to be random between patients

Change in SGI Score

Estimated via a MMRM with change from baseline (Day 1, Part 2), Day 8, and Day 14 as the dependent variable and terms for treatment, time (Day 8, Day 14), treatment-by-time interaction, and double-blind baseline T25FW walking speed as fixed effects and patient as a random effect. The model assumed time effect to be random between patients.

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

Estimated via a MMRM with change from baseline (Day 1, Part 2), Day 8, and Day 14 as the dependent variable and terms for treatment, time (Day 8, Day 14), treatment-by-time interaction as fixed effects and patient as a random effect. The model assumed time effect to be random between patients

Spots Global Cancer Trial Database for A Phase 3 Study of Amifampridine Phosphate in Patients With Lambert Eaton Myasthenic Syndrome (LEMS)

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