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Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (Mexiletine-2)

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: NCT02781454
Recruitment Status : Completed
First Posted : May 24, 2016
Results First Posted : December 5, 2019
Last Update Posted : December 5, 2019
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Michael D Weiss, University of Washington

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Sporadic Amyotrophic Lateral Sclerosis
Interventions Drug: Mexiletine
Drug: Placebo
Enrollment 20
Recruitment Details Subjects were enrolled at 9 Northeast ALS Consortium (NEALS) centers in the US. These NEALS centers were academic clinical research centers with established practices where sporadic ALS (sALS) patients are regularly seen and treated.
Pre-assignment Details Within 21 days prior to treatment assignment, patients were screened for eligibility based on inclusion/exclusion criteria. Failure to meet any of these criteria at the time of this screening would result in exclusion from the study, and these patients would not be assigned to a treatment group.
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Period Title: Overall Study
Started 8 6 6
Completed 8 6 5
Not Completed 0 0 1
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo Total
Hide Arm/Group Description

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 8 6 6 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 6 participants 6 participants 20 participants
58.5  (10.8) 60.5  (14.1) 52.0  (11.3) 57.2  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 20 participants
Female
3
  37.5%
2
  33.3%
1
  16.7%
6
  30.0%
Male
5
  62.5%
4
  66.7%
5
  83.3%
14
  70.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 20 participants
Hispanic or Latino
0
   0.0%
1
  16.7%
0
   0.0%
1
   5.0%
Not Hispanic or Latino
8
 100.0%
5
  83.3%
6
 100.0%
19
  95.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 20 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
8
 100.0%
6
 100.0%
6
 100.0%
20
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 8 participants 6 participants 6 participants 20 participants
8
 100.0%
6
 100.0%
6
 100.0%
20
 100.0%
El Escorial Diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 20 participants
Possible
1
  12.5%
0
   0.0%
3
  50.0%
4
  20.0%
Prob Lab Supported
5
  62.5%
5
  83.3%
2
  33.3%
12
  60.0%
Probable
2
  25.0%
0
   0.0%
1
  16.7%
3
  15.0%
Definite
0
   0.0%
1
  16.7%
0
   0.0%
1
   5.0%
[1]
Measure Description: Participants were classified according to the El Escorial World Federation of Neurology Criteria for the Diagnosis of ALS (Brooks J Neurol Sci 1994) based on the extent of ALS disease signs and symptoms consistent with neurodegeneration of upper and lower motor neurons
1.Primary Outcome
Title Change in Resting Motor Threshold
Hide Description The resting motor threshold (RMT) assessed from single pulse transcranial magnetic stimulation (TMS) measurements made before treatment, after 4 weeks of treatment, and then again after a 4 week washout, was used as the primary pharmacodynamic marker of cortical hyperexcitability. RMT is the stimulus intensity required to produce and maintain a 0.2 mV peak-to-peak motor evoked potential of the abductor pollicis brevis muscle by TMS. A smaller RMT is thought to suggest greater neuronal excitability.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 and from Week 4 to Week 8 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Least Squares Mean (Standard Error)
Unit of Measure: percentage of maximum stimulus output
change from baseline to week 4 -2.430  (2.323) 0.805  (2.207) 4.746  (2.185)
change from week 4 to week 8 1.465  (2.357) -0.284  (2.169) -2.908  (2.247)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo for change from baseline to week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value -5.558
Confidence Interval (2-Sided) 95%
-10.80 to -0.315
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Effect on Short-interval Intracortical Inhibition
Hide Description Short-interval intracortical inhibition (SICI) is a measure of neuronal excitability measured by dual pulse TMS with a conditioned (80% of RMT) and test pulses (120% of RMT) to generate a stable MEP amplitude of 0.2 mV, averaged over interstimulus intervals of 1-7 ms. It is thought to reflect refractory cortical axons and subsequent resynchronization of cortico-cortical and corticomotoneuronal volleys or activation of non-GABAergic cortical inhibitory circuits (initial phase) and synaptic neurotransmission through GABAA receptors (second phase). The value for SICI thought to be maximally sensitive for detecting in changes in ALS subjects compared to controls is is derived by measuring the motor evoked potential amplitude (MEP) at an interstimulus interval of 3 ms (ISI 3 ms) and normalizing to the MEP amplitude at 120% of the resting motor threshold (MEP 120% RMT). A reduction in SICI reflecting greater excitability would generate a larger ratio of MEP ISI 3 ms/MEP 120% RMT.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: unitless ratio MEP ISI 3 ms/MEP 120% RMT
0.655
(0.437 to 0.983)
0.886
(0.608 to 1.291)
0.961
(0.634 to 1.459)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo ratio of week 4 to week 0
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.332
Comments linear contrast active vs placebo
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value 0.792
Confidence Interval (2-Sided) 95%
0.484 to 1.296
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Motor Evoked Potential Amplitude
Hide Description The motor evoked potential (MEP) amplitude is taken from single pulse transcranial magnetic stimulation (TMS) and reflects the density of corticomotoneuronal projections onto motor neurons and is affected by cortical hyperexcitability early in ALS where it is thought to be larger than age-matched controls and axonal degeneration later in the disease when it decreases in amplitude. The MEP is most reliable in assessing cortical motor neuronal preservation and excitability when normalized to the peak compound nerve action potential (CMAP) amplitude which reflects the integrity of peripheral motor nerve axons. It is also normalized here to 120% of the RMT to derive a ratio of MEP at 120% RMT/peak CMAP.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
MEP at 120% RMT/peak CMAP
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: unitless ratio of ms/ms
0.589
(0.315 to 1.102)
0.490
(0.249 to 0.965)
1.308
(0.695 to 2.462)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo ratio of week 4 to week 0
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value 0.411
Confidence Interval (2-Sided) 95%
0.208 to 0.810
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Effect on Cortical Silent Period
Hide Description The cortical silent period (CSP) is recorded with single pulse TMS as a duration from the onset of the MEP response to resumption of voluntary electromyography activity with the patient performing a voluntary contraction, set to 30% of maximal voluntary contraction. A shorter CSP compared to controls would reflect greater excitability.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: milliseconds
3.937
(-31.75 to 39.624)
4.823
(-29.76 to 39.408)
4.037
(-30.84 to 38.911)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo for change from baseline to week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.986
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value 0.343
Confidence Interval (2-Sided) 95%
-41.36 to 42.042
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Effect on Strength Duration Time Constant
Hide Description The strength duration time constant (SDTC) is used in threshold tracking nerve axonal excitability studies and is interpreted as a measure of axonal excitability that is dependent upon the biophysical properties of the axonal membrane at the node of Ranvier, especially persistent sodium current. It is derived from the relationship between stimulus duration and intensity. A higher SDTC would reflect greater excitability of motor nerve axons.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
strength duration time constant
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: milliseconds
0.895
(0.802 to 0.998)
0.966
(0.848 to 1.099)
0.935
(0.837 to 1.045)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo ratio of week 4 to week 0
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.915
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value 0.994
Confidence Interval (2-Sided) 95%
0.876 to 1.126
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Effect on Depolarizing Threshold Electrotonus (90-100 ms)
Hide Description Depolarizing threshold electrotonus (90-100 ms) (TEd 90-100 ms) is used in threshold tracking nerve axonal excitability studies in which long-lasting subthreshold depolarizing currents are generated, measured at 90-100 ms following the stimulus. This measure is associated with a decrease in the membrane excitability threshold due to opening of potassium channels on the axonal membrane. Intrinsic changes in axonal excitability properties, such as thought to occur in ALS, could possibly alter this measure, presumably by decreasing TEd 90-100 ms more substantially than normal.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of threshold depolarization
-0.140
(-4.925 to 4.645)
4.005
(-1.375 to 9.384)
0.844
(-3.735 to 5.423)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo for change from baseline to week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.694
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value 1.089
Confidence Interval (2-Sided) 95%
-4.609 to 6.786
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Effect on Hyperpolarizing Threshold Electrotonus (90-100 ms)
Hide Description Hyperpolarizing threshold electrotonus (90-100 ms) (TEh 90-100 ms) is used in threshold tracking nerve axonal excitability studies in which long-lasting subthreshold hyperpolarizing currents are generated, measured at 90-100 ms following the stimulus. This measure is associated with an increase in the membrane excitability threshold due to closure of potassium channels causing increased resistance of the internodal axonal membrane. Intrinsic changes in axonal excitability properties, such as thought to occur in ALS, could possibly alter this measure.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage threshold hyperpolarization
-10.184
(-21.57 to 1.204)
2.230
(-10.52 to 14.979)
-4.219
(-15.00 to 6.562)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo for change from baseline to week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.969
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value 0.242
Confidence Interval (2-Sided) 95%
-12.64 to 13.126
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Effect on Superexcitability
Hide Description Superexcitability is a component of recovery cycle analysis assessing motor axonal excitability, employing threshold tracking nerve conduction study. It is a depolarizing afterpotential measured following a single supramaximal stimulus followed by a second smaller stimulus of variable intensity and reflects passive depolarization of the internodal axon.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of threshold change
2.234
(-2.129 to 6.597)
1.511
(-3.391 to 6.413)
-0.724
(-4.974 to 3.526)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo for change from baseline to week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.323
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value 2.597
Confidence Interval (2-Sided) 95%
-2.772 to 7.966
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Effect on Subexcitability
Hide Description Subexcitability is a component of recovery cycle analysis assessing motor axonal excitability, employing threshold tracking nerve conduction study. It is a late hyperpolarizing after potential measured following a single supramaximal stimulus followed by a second smaller stimulus of variable intensity and is related to the very slow turn-off of slow potassium channels.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of threshold change
-2.563
(-5.706 to 0.581)
-0.575
(-4.178 to 3.027)
0.448
(-3.001 to 3.897)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo for change from baseline to week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.273
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value -2.017
Confidence Interval (2-Sided) 95%
-5.767 to 1.733
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Effect on Frequency of Muscle Cramps
Hide Description Will be assessed using a daily muscle cramps diary tabulated weekly beginning at Baseline.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; comparisons of treatments at Weeks 3-4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: muscle cramps/week
3.430
(1.152 to 10.210)
1.987
(0.686 to 5.755)
3.774
(0.687 to 20.740)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.713
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value 0.708
Confidence Interval (2-Sided) 95%
0.111 to 4.535
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Effect on Frequency of Fasciculations (Muscle Twitching)
Hide Description Will be assessed using a daily fasciculations diary tabulated as a percentage of days from weeks 3-4.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; comparisons of treatments at Weeks 3-4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Median (Inter-Quartile Range)
Unit of Measure: percentage of days with fasciculations
100
(83.3 to 100)
100
(100 to 100)
100
(100 to 100)
12.Other Pre-specified Outcome
Title Change in the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised
Hide Description The Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) is an instrument for evaluating the functional status of patients with ALS that includes functions related to speech, swallowing, salivation, fine motor control, gross motor function, and respiration. The score is the sum of 12 items (range 0 to 48) with higher scores reflecting better function.
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-1.414
(-2.554 to -0.274)
-1.038
(-2.352 to 0.276)
-0.827
(-2.141 to 0.487)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo for change from baseline to week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.601
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value -0.399
Confidence Interval (2-Sided) 95%
-1.966 to 1.169
Estimation Comments [Not Specified]
13.Other Pre-specified Outcome
Title Change in Slow Vital Capacity
Hide Description Measure of decline in respiratory muscle strength
Time Frame Accessed at Screening, Baseline, Week 4, and Week 8; change from Baseline to Week 4 reported
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description:

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

Overall Number of Participants Analyzed 8 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: maximum percent predicted
-0.532
(-4.425 to 3.361)
-6.918
(-11.370 to -2.461)
-0.991
(-5.450 to 3.467)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, 300 Milligrams, Mexiletine, 600 Milligrams, Placebo
Comments Comparison of active (300 and 600 mg) vs placebo for change from baseline to week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.285
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter linear contrast active vs placebo
Estimated Value -2.734
Confidence Interval (2-Sided) 95%
-7.938 to 2.471
Estimation Comments [Not Specified]
Time Frame 8 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Hide Arm/Group Description

Mexiletine, 300 milligrams by mouth per day for 4 weeks.

Mexiletine

Mexiletine, 600 milligrams by mouth per day for 4 weeks.

Mexiletine

Placebo, by mouth per day for 4 weeks.

Placebo

All-Cause Mortality
Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)      0/6 (0.00%)      0/6 (0.00%)    
Hide Serious Adverse Events
Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/8 (0.00%)      0/6 (0.00%)      1/6 (16.67%)    
Vascular disorders       
Deep vein thrombosis *  0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Mexiletine, 300 Milligrams Mexiletine, 600 Milligrams Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/8 (62.50%)      5/6 (83.33%)      5/6 (83.33%)    
Ear and labyrinth disorders       
Inner ear signs and symptoms *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Gastrointestinal disorders       
Dental pain and sensation disorders *  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Diarrhoea (excl infective) *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Dyspeptic signs and symptoms *  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Gastrointestinal atonic and hypomotility disorders NEC *  0/8 (0.00%)  0 2/6 (33.33%)  2 3/6 (50.00%)  3
Nausea and vomiting symptoms *  0/8 (0.00%)  0 2/6 (33.33%)  2 1/6 (16.67%)  1
Oral dryness and saliva altered *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Oral soft tissue pain and paraesthesia *  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
General disorders       
General signs and symptoms NEC *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Implant and catheter site reactions *  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Oedema NEC *  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Asthenic *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Infections and infestations       
Lower respiratory tract and lung infections *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Injury, poisoning and procedural complications       
Non-site specific injuries NEC *  0/8 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Muscle pains *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Muscle related signs and symptoms NEC *  1/8 (12.50%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Musculoskeletal and connective tissue signs and symptoms NEC *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Nervous system disorders       
Headaches NEC *  1/8 (12.50%)  1 2/6 (33.33%)  2 0/6 (0.00%)  0
Neurological signs and symptoms NEC *  2/8 (25.00%)  2 1/6 (16.67%)  1 1/6 (16.67%)  1
Speech and language abnormalities *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Tremor (excl congenital) *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Psychiatric disorders       
Disturbances in initiating and maintaining sleep *  0/8 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Renal and urinary disorders       
Bladder and urethral symptoms *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Breathing abnormalities *  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Upper respiratory tract signs and symptoms *  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders       
Erythemas *  2/8 (25.00%)  5 1/6 (16.67%)  3 2/6 (33.33%)  8
Rashes, eruptions and exanthems NEC *  1/8 (12.50%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Vascular disorders       
Peripheral embolism and thrombosis *  0/8 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Dr. Michael D. Weiss
Organization: University of Washington
Phone: 206-598-7688
EMail: mdweiss@uw.edu
Layout table for additonal information
Responsible Party: Michael D Weiss, University of Washington
ClinicalTrials.gov Identifier: NCT02781454    
Other Study ID Numbers: MX-ALS-002
First Submitted: May 10, 2016
First Posted: May 24, 2016
Results First Submitted: October 6, 2019
Results First Posted: December 5, 2019
Last Update Posted: December 5, 2019