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Phase 3 Study to Evaluate Efficacy of Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02970162
Recruitment Status : Completed
First Posted : November 21, 2016
Results First Posted : December 24, 2018
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Catalyst Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Lambert-Eaton Myasthenic Syndrome
Interventions Drug: Amifampridine Phosphate
Drug: Placebo Oral Tablet
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Hide Arm/Group Description

amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days

Amifampridine Phosphate

placebo by mouth 3 to 4 times per day for 4 days

Placebo Oral Tablet

Period Title: Overall Study
Started 13 13
Completed 13 13
Not Completed 0 0
Arm/Group Title Amifampridine Phosphate Placebo (for Amifampridine Phosphate) Total
Hide Arm/Group Description

amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days

Amifampridine Phosphate

placebo by mouth 3 to 4 times per day for 4 days

Placebo Oral Tablet

Total of all reporting groups
Overall Number of Baseline Participants 13 13 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 13 participants 26 participants
54.9  (11.51) 53.4  (13.46) 54.2  (12.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Female
7
  53.8%
9
  69.2%
16
  61.5%
Male
6
  46.2%
4
  30.8%
10
  38.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Hispanic or Latino
4
  30.8%
1
   7.7%
5
  19.2%
Not Hispanic or Latino
9
  69.2%
12
  92.3%
21
  80.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 13 participants 13 participants 26 participants
77.62  (20.312) 93.95  (15.449) 85.78  (19.545)
1.Primary Outcome
Title Quantitative Myasthenia Gravis (QMG) Score
Hide Description The QMG is a physician-rated test including 13 assessments such as facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each assessment is graded as 0 (none), 1 (mild), 2 (moderate), or 3 (severe), for a total range of 0-39. A higher total score indicates a worse outcome.
Time Frame change from baseline in QMG score at end of day 4
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Hide Arm/Group Description:

amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days

Amifampridine Phosphate

placebo by mouth 3 to 4 times per day for 4 days

Placebo Oral Tablet

Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 7.8  (4.20) 8.5  (5.43)
Day 4 7.9  (4.94) 15.0  (5.90)
Change from baseline 0.1  (3.07) 6.5  (4.82)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Amifampridine Phosphate, Placebo (for Amifampridine Phosphate)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments LS means
Method Least square means
Comments Fixed effects treatment and QMG at Baseline. Between-treatment difference in LS means (95% CI) -6.54 (-9.78, -3.29).
2.Primary Outcome
Title Subject Global Impression (SGI) Score
Hide Description The SGI is a 7-point scale on which the patient rates their global impression of the effects of a study treatment (1=terrible to 7=delighted). The SGI was assessed by the patient or the patient's parent/guardian/caregiver if the patient was unable to complete the SGI. The SGI has demonstrated concordance with the physician's assessment of improvement.
Time Frame change from baseline in SGI score at end of day 4
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Hide Arm/Group Description:

amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days

Amifampridine Phosphate

placebo by mouth 3 to 4 times per day for 4 days

Placebo Oral Tablet

Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 6.1  (0.86) 5.8  (0.90)
Day 4 5.3  (1.65) 2.4  (1.76)
Change from baseline to Day 4 -0.8  (1.74) -3.5  (2.18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Amifampridine Phosphate, Placebo (for Amifampridine Phosphate)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments CFB for SGI score was modeled as the response, with fixed effects terms for treatment and SGI at Baseline
Method Fixed effects linear model
Comments This statistical test applies to the change from baseline SGI scores to Day 4 values row.
Method of Estimation Estimation Parameter LS means
Estimated Value 2.95
Confidence Interval (2-Sided) 95%
1.53 to 4.38
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Clinician's Global Impression of Improvement (CGI-I) at Day 4 Compared to Baseline
Hide Description The CGI-I captures the Investigator's global impression of the patient's improvement or worsening from baseline status. The 7-point scale is scored by the Investigator based on changes in symptoms, behavior, and functional abilities. Each symptom is rated as 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), or 7 (very much worse). The total score can range from 0 to 49. A higher score indicates a worse outcome.
Time Frame change from baseline in CGI-I score at end of day 4
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Hide Arm/Group Description:

amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days

Amifampridine Phosphate

placebo by mouth 3 to 4 times per day for 4 days

Placebo Oral Tablet

Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: scores on a scale
3.8  (0.8) 5.5  (1.27)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Amifampridine Phosphate, Placebo (for Amifampridine Phosphate)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
4.Other Pre-specified Outcome
Title Triple Timed Up and Go Walk Test (3TUG)
Hide Description The 3TUG is a functional mobility test that requires a patient to stand up from a straight-backed armchair, walk 3 meters, turn around, walk back, and sit down in the chair. A modification of this is where the individual performs the test 3 times without pause, and the measurement is the average time required to complete each of the 3 repetitions. Based upon literature reports that a significant change in gait for a similar walk-test is an increase in time of more than 20%, this has been incorporated into the endpoint.
Time Frame change from baseline in 3TUG at end of day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The number and proportion of patients with a ≥20% increase in 3TUG average time
Arm/Group Title Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Hide Arm/Group Description:

amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days

Amifampridine Phosphate

placebo by mouth 3 to 4 times per day for 4 days

Placebo Oral Tablet

Overall Number of Participants Analyzed 13 13
Measure Type: Count of Participants
Unit of Measure: Participants
1
   7.7%
8
  61.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Amifampridine Phosphate, Placebo (for Amifampridine Phosphate)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0112
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient).
Adverse Event Reporting Description Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
 
Arm/Group Title Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Hide Arm/Group Description

amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days

Amifampridine Phosphate

placebo by mouth 3 to 4 times per day for 4 days

Placebo Oral Tablet

All-Cause Mortality
Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/13 (0.00%) 
Hide Serious Adverse Events
Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/13 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Amifampridine Phosphate Placebo (for Amifampridine Phosphate)
Affected / at Risk (%) Affected / at Risk (%)
Total   3/13 (23.08%)   10/13 (76.92%) 
Cardiac disorders     
atrial fibrillation  1  0/13 (0.00%)  1/13 (7.69%) 
myocardial ischemia  1  0/13 (0.00%)  4/13 (30.77%) 
Ear and labyrinth disorders     
motion sickness  1  0/13 (0.00%)  1/13 (7.69%) 
Eye disorders     
diplopia  1  0/13 (0.00%)  1/13 (7.69%) 
eyelid ptosis  1  0/13 (0.00%)  1/13 (7.69%) 
Gastrointestinal disorders     
dry mouth  1  0/13 (0.00%)  2/13 (15.38%) 
diarrhoea  1  0/13 (0.00%)  1/13 (7.69%) 
dysphagia  1  0/13 (0.00%)  1/13 (7.69%) 
hypoaesthesia, oral  1  0/13 (0.00%)  1/13 (7.69%) 
impaired gastric emptying  1  0/13 (0.00%)  1/13 (7.69%) 
nausea  1  0/13 (0.00%)  1/13 (7.69%) 
oral disorder  1  0/13 (0.00%)  1/13 (7.69%) 
vomiting  1  0/13 (0.00%)  1/13 (7.69%) 
asthenia  1  0/13 (0.00%)  2/13 (15.38%) 
General disorders     
fatigue  1  0/13 (0.00%)  4/13 (30.77%) 
feeling hot  1  0/13 (0.00%)  2/13 (15.38%) 
gait disturbance  1  0/13 (0.00%)  1/13 (7.69%) 
pain  1  0/13 (0.00%)  1/13 (7.69%) 
Infections and infestations     
bronchitis  1  0/13 (0.00%)  1/13 (7.69%) 
Metabolism and nutrition disorders     
decreased appetite  1  0/13 (0.00%)  1/13 (7.69%) 
Musculoskeletal and connective tissue disorders     
muscular weakness  1  0/13 (0.00%)  5/13 (38.46%) 
limb discomfort  1  0/13 (0.00%)  2/13 (15.38%) 
muscle spasm  1  0/13 (0.00%)  2/13 (15.38%) 
arthralgia  1  0/13 (0.00%)  1/13 (7.69%) 
back pain  1  1/13 (7.69%)  0/13 (0.00%) 
musculoskeletal stiffness  1  0/13 (0.00%)  1/13 (7.69%) 
pain in extremity  1  1/13 (7.69%)  0/13 (0.00%) 
Nervous system disorders     
balance disorder  1  0/13 (0.00%)  2/13 (15.38%) 
eyelid ptosis  1  0/13 (0.00%)  1/13 (7.69%) 
facial nerve disorder  1  0/13 (0.00%)  1/13 (7.69%) 
headache  1  1/13 (7.69%)  0/13 (0.00%) 
movement disorder  1  0/13 (0.00%)  1/13 (7.69%) 
somnolence  1  0/13 (0.00%)  1/13 (7.69%) 
speech disorder  1  0/13 (0.00%)  1/13 (7.69%) 
Psychiatric disorders     
insomnia  1  0/13 (0.00%)  1/13 (7.69%) 
Respiratory, thoracic and mediastinal disorders     
dysphonia  1  0/13 (0.00%)  1/13 (7.69%) 
dyspnoea  1  0/13 (0.00%)  1/13 (7.69%) 
Skin and subcutaneous tissue disorders     
dermatitis contact  1  0/13 (0.00%)  1/13 (7.69%) 
1
Term from vocabulary, MedDRA 13.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gary Ingenito
Organization: Catalyst Pharmaceuticals, Inc.
Phone: 305-420-3200
EMail: gingenito@catalystpharma.com
Layout table for additonal information
Responsible Party: Catalyst Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02970162    
Other Study ID Numbers: LMS-003
First Submitted: November 16, 2016
First Posted: November 21, 2016
Results First Submitted: September 24, 2018
Results First Posted: December 24, 2018
Last Update Posted: December 24, 2018