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Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia

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: NCT00832000
Recruitment Status : Completed
First Posted : January 29, 2009
Results First Posted : March 11, 2013
Last Update Posted : August 23, 2013
Sponsor:
Information provided by (Responsible Party):
Richard Barohn, MD, University of Kansas Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Myotonia
Non-Dystrophic Myotonia
Interventions Drug: Mexiletine
Drug: Placebo
Enrollment 59
Recruitment Details Eligible participants were at least 16 years of age, had clinical symptoms or signs of NDM, and myotonic potentials on electromyography. Participants were either enrolled in the CINCH NDM Natural History Study, or a new patient with genetically confirmed NDM, or with clinical features of NDM but negative myotonic dystrophy DNA testing.
Pre-assignment Details Patients taking anti-myotonic agents were required to discontinue medications for a wash-out period equal to 7 times the half-life of elimination prior to their baseline visit. Participants were ineligible if they has specific contraindications to taking mexiletine (cardiac conduction defects, hepatic or renal disease, or heart failure).
Arm/Group Title Mexiletine Then Placebo Placebo Then Mexiletine
Hide Arm/Group Description

29 Participants will receive mexiletine for 4 weeks, then no intervention for 1 week, and finally placebo for 4 weeks.

Included in anaysis*: 28 patients

*Modified intention to treat analysis. 1 subject in each group not included in primary analysis due to failure to make any calls to the IVR system for stiffness in either period

30 Participants will receive placebo for 4 weeks, then no intervention for 1 week, and finally mexiletine for 4 weeks.

Included in analysis* 29 patients

*Modified intention to treat analysis. 1 subject in each not included in primary analysis due to failure to make any calls to the IVR system for stiffness in either period.
Period Title: Overall Study
Started 29 [1] 30 [2]
Crossed Over to Opposite Intervention 25 [2] 29 [1]
Completed 23 29
Not Completed 6 1
Reason Not Completed
Adverse Event             2             0
Withdrawal by Subject             1             0
No calls to IVR in either period             1             1
No calls to IVR in period 2             2             0
[1]
Mexiletine 200 mg orally three times daily
[2]
Placebo
Arm/Group Title All Study Participants
Hide Arm/Group Description All participants received all inerventions; therefore, we combined all participants into one Arm/Group.
Overall Number of Baseline Participants 59
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
<=18 years
1
   1.7%
Between 18 and 65 years
56
  94.9%
>=65 years
2
   3.4%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 59 participants
42.9  (25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
Female
26
  44.1%
Male
33
  55.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 59 participants
United States 31
Canada 4
United Kingdom 12
Italy 12
1.Primary Outcome
Title Patient-reported Stiffness on the IVR
Hide Description Stiffness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of stiffness for each participant was calculated from daily calls made in weeks 3-4 of each period.
Time Frame Weeks 3-4 of each period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intention to treat analysis (n=57). 2 subjects were excluded from analysis due to failure call the IVR system in either period. Treatment group estimates by period are taken from the mixed model, the number above reflecting the number who contributed to the model point estimate. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine - Period 1 Placebo - Period 1 Mexiletine - Period 2 Placebo - Period 2
Hide Arm/Group Description:
Mexiletine capsules 200 mg orally three times daily period 1. Due to an interaction between period and treatment the primary outcome was presented separately for periods 1 and 2.
Placebo capsules orally three times dailyperiod 1. Due to an interaction between period and treatment the primary outcome was presented separately for periods 1 and 2.
Mexiletine capsules 200 mg orally three times daily period 2. Due to an interaction between period and treatment the primary outcome was presented separately for periods 1 and 2.
Placebo capsules orally three times dailyperiod 2. Due to an interaction between period and treatment the primary outcome was presented separately for periods 1 and 2.
Overall Number of Participants Analyzed 28 29 29 25
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
2.53
(1.80 to 3.17)
4.21
(3.40 to 5.20)
1.60
(1.04 to 2.20)
5.27
(4.44 to 6.27)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine - Period 1, Placebo - Period 1
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model (n=57). When a carryover effect was detected, the significance level associated with the additive portion of the mexiletine effect (labeled period 1) is followed by the level associated with the interaction of mexiletine and period 2 (labeled period 2). All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.68
Confidence Interval (2-Sided) 95%
-2.66 to -0.706
Parameter Dispersion
Type: Standard Deviation
Value: 1.24
Estimation Comments Residual standard deviation.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Mexiletine - Period 2, Placebo - Period 2
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model (n=57). When a carryover effect was detected, the significance level associated with the additive portion of the mexiletine effect (labeled period 1) is followed by the level associated with the interaction of mexiletine and period 2 (labeled period 2). All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.68
Confidence Interval 95%
-3.85 to -0.139
Parameter Dispersion
Type: Standard Deviation
Value: 1.24
Estimation Comments Residual standard deviation.
2.Secondary Outcome
Title Patient Reported Pain on the IVR
Hide Description Pain measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of pain for each participant was calculated from daily calls made in weeks 3-4 of each period.
Time Frame Weeeks 3-4 of each period
Hide Outcome Measure Data
Hide Analysis Population Description
48 partipants who experienced pain in either period 1 or period 2 were included in analysis. All treatment group means are extracted from the mixed effects model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Participants experiencing pain on mexiletine capsules 200 mg orally three times daily in period 1 or period 2
Participants experiencing pain on placebo capsules orally three times dailyin period 1 or period 2
Overall Number of Participants Analyzed 48 48
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
1.54
(0.924 to 2.13)
3.17
(2.43 to 3.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. When a carryover effect was detected, the significance level associated with the additive portion of the mexiletine effect (labeled period 1) is followed by the level associated with the interaction of mexiletine and period 2 (labeled period 2). All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.63
Confidence Interval (2-Sided) 95%
-2.00 to -1.26
Parameter Dispersion
Type: Standard Deviation
Value: 1.19
Estimation Comments Residual standard deviation.
3.Secondary Outcome
Title Patient Reported Weakness on the IVR
Hide Description Weakness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of weakness for each participant was calculated from daily calls made in weeks 3-4 of each period.
Time Frame Weeks 3-4 of each period
Hide Outcome Measure Data
Hide Analysis Population Description
44 partipants who experienced weakness in either period 1 or period 2 were included in analysis. All treatment group means are extracted from the mixed effects model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Particiapnts who experienced weakness on mexiletine capsules 200 mg orally three times daily in either period 1 or period 2.
Particiapnts who experienced weakness on placebo capsules orally three times daily in either period 1 or period 2.
Overall Number of Participants Analyzed 44 44
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
1.96
(1.42 to 2.63)
3.22
(2.52 to 3.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. When a carryover effect was detected, the significance level associated with the additive portion of the mexiletine effect (labeled period 1) is followed by the level associated with the interaction of mexiletine and period 2 (labeled period 2). All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.26
Confidence Interval (2-Sided) 95%
-1.67 to -0.861
Parameter Dispersion
Type: Standard Deviation
Value: 1.27
Estimation Comments Residual standard deviation.
4.Secondary Outcome
Title Patient Reported Tiredness on the IVR
Hide Description Tiredness measured on a 1-9 scale, 1 being minimal, 9 the worst ever experienced. 0=no symptom reported. For analysis the average severity of tiredness for each participant was calculated from daily calls made in weeks 3-4 of each period.
Time Frame Weeks 3-4 of each period
Hide Outcome Measure Data
Hide Analysis Population Description
49 partipants who experienced tiredness in either period 1 or period 2 were included in analysis. All treatment group means are extracted from the mixed effects model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Particiapnts who experienced tiredness on mexiletine 200 mg capsules orally three times daily in either period 1 or period 2.
Particiapnts who experienced tiredness on placebo capsules orally three times daily in either period 1 or period 2.
Overall Number of Participants Analyzed 49 49
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
2.90
(2.12 to 3.68)
3.82
(3.03 to 4.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. When a carryover effect was detected, the significance level associated with the additive portion of the mexiletine effect (labeled period 1) is followed by the level associated with the interaction of mexiletine and period 2 (labeled period 2). All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.918
Confidence Interval (2-Sided) 95%
-1.30 to -0.532
Parameter Dispersion
Type: Standard Deviation
Value: 1.29
Estimation Comments Residual standard deviation.
5.Secondary Outcome
Title Quantitative Measure of Hand Grip Myotonia (Seconds)
Hide Description Maximum voluntary contractions following forced right hand grip were recorded and the time to relax from 90% to 5% of average maximal force was determined using automated analysis software.
Time Frame The end of period 1 (week 4) and period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with quantitative handgrip myotonia values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is a geometric-like mean using log (t+0.1) 'normalizing' transformation. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Average 90% to 5% hand grip relaxation time for particpants receiving mexiletine 200 mg capsules orally three times daily either in period 1 or period 2
Average 90% to 5% hand grip relaxation time for particpants receiving placebo capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 54 54
Mean (95% Confidence Interval)
Unit of Measure: seconds
0.321
(0.274 to 0.370)
0.429
(0.365 to 0.517)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.109
Confidence Interval (2-Sided) 95%
-0.177 to -0.056
Parameter Dispersion
Type: Standard Deviation
Value: 0.563
Estimation Comments Residual standard deviation.
6.Secondary Outcome
Title Compound Motor Action Potentials After Short Exercise Test
Hide Description The maximal post-exercise compound muscle action potential (CMAP) after short periods of exercise as a percent of the baseline measurement.
Time Frame The end of period 1 (week 4) and period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with short exercise test values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is taken from the mixed model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Post exercise CMAP amplitude (as a percent of baseline measurement) for particpants receiving mexiletine capsules 200 mg orally three times daily either in period 1 or period 2
Post exercise CMAP amplitude (as a percento f baseline measurement) for particpants receiving mexiletine capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 56 56
Mean (95% Confidence Interval)
Unit of Measure: percentage of baseline CMAP amplitude
83.1
(77.5 to 88.4)
78.6
(71.9 to 84.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.54
Confidence Interval (2-Sided) 95%
-0.680 to 9.75
Parameter Dispersion
Type: Standard Deviation
Value: 13.1
Estimation Comments Residual standard deviation.
7.Secondary Outcome
Title Graded Myotonia by Needle Electromyography - Right Abductor Digiti Minimi
Hide Description Measured the amount of myotonia present on needle exam by assigning a number 1-3, with 1 being minimal amount of myotonia on needle stick and 3 being maximal amount of myotonia present on needle stick.
Time Frame The end of period 1 (week 4) and period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with graded needle EMG of the RADM values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is taken from the mixed model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Graded myotonia in right ADM for particpants receiving mexiletine capsules 200 mg orally three times daily either in period 1 or period 2
Graded myotonia in right ADM for particpants receiving placebo capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 56 56
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
2.05
(1.75 to 2.33)
2.62
(2.39 to 2.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wilcoxon test associated with mexiletine effect from the linear mixed effects model. The Wilcoxon test was substituted because the outcome is not continuous and therefore normality of the residuals is not satisfied. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.568
Confidence Interval (2-Sided) 95%
-0.812 to -0.325
Parameter Dispersion
Type: Standard Deviation
Value: 0.600
Estimation Comments Residual standard deviation.
8.Secondary Outcome
Title Clinical Hand Grip Myotonia Evaluation (Seconds)
Hide Description The time to open the fist after a forced handgrip as measured on a stopwatch.
Time Frame The end of period 1 (week 4) and the end of period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with clinical handgrip myotonia values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is a geometric-like mean. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Average time to open the fist after forced hand grip for particpants receiving mexiletine 200 mg capsules orally three times daily either in period 1 or period 2
Average time to open the fist after forced hand grip for particpants receiving placebo capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 57 57
Mean (95% Confidence Interval)
Unit of Measure: Seconds
0.164
(0.0858 to .294)
0.494
(0.281 to 0.872)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.330
Confidence Interval (2-Sided) 95%
-0.633 to -0.142
Parameter Dispersion
Type: Standard Deviation
Value: 1.083
Estimation Comments Residual standard deviation.
9.Secondary Outcome
Title Clinical Eye Closure Myotonia Evaluation (Seconds)
Hide Description Time to open the eyes after forced eye closure as measured on a stopwatch.
Time Frame The end of period 1 (week 4) and the end of period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with clinical eye closure myotonia values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is a geometric-like mean. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Average time to open eyes after forced eye closure for particpants receiving mexiletine 200 mg capsules orally three times daily either in period 1 or period 2
Average time to open eyes after forced eye closure for particpants receiving placebo capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 57 57
Mean (95% Confidence Interval)
Unit of Measure: Seconds
0.161
(0.0704 to 0.314)
0.474
(0.261 to 0.871)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.313
Confidence Interval (2-Sided) 95%
-0.602 to -0.149
Parameter Dispersion
Type: Standard Deviation
Value: 0.889
Estimation Comments Residual standard deviation.
10.Secondary Outcome
Title Graded Myotonia by Needle Electromyography - Right Tibialis Anterior
Hide Description Measured the amount of myotonia present on needle exam by assigning a number 1-3, with 1 being minimal amount of myotonia on needle stick and 3 being maximal amount of myotonia present on needle stick.
Time Frame The end of period 1 (week 4) and period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with graded needle EMG of the RTA values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is taken from the mixed model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Graded myotonia in right TA for particpants receiving mexiletine capsules 200 mg orally three times daily either in period 1 or period 2
Graded myotonia in right ADM for particpants receiving placebo capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 56 56
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
2.07
(1.73 to 2.37)
2.54
(2.28 to 2.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wilcoxon test associated with mexiletine effect from the linear mixed effects model. The Wilcoxon test was substituted because the outcome is not continuous and therefore normality of the residuals is not satisfied. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.464
Confidence Interval (2-Sided) 95%
-0.675 to -0.254
Parameter Dispersion
Type: Standard Deviation
Value: 0.516
Estimation Comments Residual standard deviation.
11.Secondary Outcome
Title Compound Motor Action Potentials After Long Exercise Test
Hide Description Compound muscle action potential (CMAP) after long periods of exercise as a percentage of baseline.
Time Frame The end of period 1 (week 4) and period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with long exercise test values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is taken from the mixed model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Post exercise CMAP amplitude (as a percentage of baseline measreument) for participants receiving mexiletine capsules 200 mg orally three times daily either in period 1 or period 2
Post exercise CMAP amplitude ( as a percentage of baseline measurement) for participants receiving placebo capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 56 56
Mean (95% Confidence Interval)
Unit of Measure: percentage of baseline CMAP amplitude
81.8
(76.8 to 87.0)
80.1
(74.7 to 86.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.69
Confidence Interval (2-Sided) 95%
-3.34 to 6.73
Parameter Dispersion
Type: Standard Deviation
Value: 12.6
Estimation Comments Residual standard deviation.
12.Secondary Outcome
Title Individualized Neuromuscular Quality of Life Scale - Summary Score
Hide Description Quality of life scale for patinets with neuromuscular disorders. The INQoL summary score is a weighted average made up of 5 subdomains (activities, social relationships, independence, emotions, and body image) which document the impact of a disease on a patients' quality of life. Scores range from 0-100, and can be interpreted as the percent of maximal detrimental impact on quality of life. A higher score indicates more detrimental impact.
Time Frame The end of period 1 (week 4) and period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with INQoL summary score values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is taken from the mixed model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
INQoL summary score for participants receiving mexiletine capsules 200 mg orally three times daily either in period 1 or period 2
INQoL summary score for participants receiving placebo capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 51 51
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
14.0
(11.6 to 16.5)
16.7
(14.0 to 19.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.69
Confidence Interval (2-Sided) 95%
-4.07 to -1.30
Parameter Dispersion
Type: Standard Deviation
Value: 3.44
Estimation Comments Residual standard deviation.
13.Secondary Outcome
Title Short Form 36 - Physical Composite Score
Hide Description The SF-36 is a standard quality of life instrument. The physical composite score represents the the physical burden on quality of life and is a summary of questions related to physical impact of a disease or condition (physical function, role physical, bodily pain, and general health). The score is nomralized to the population and ranges from 0-100, with the US normal value of 50. A lower score represents a greater impact of quality of life.
Time Frame Particiapnts who experienced weakness on mexiletine in either period 1 or period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with SF-36 physical composite values in either period 1 or period 2 were included in analysis. The treatment-specific group mean is taken from the mixed model. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
SF-36 physical composite score for participants receiving mexiletine capsules 200 mg orally three times daily either in period 1 or period 2
SF-36 physical composite score for participants receiving placebo capsules orally three times daily either in period 1 or period 2
Overall Number of Participants Analyzed 57 57
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
44.8
(41.9 to 47.4)
39.2
(35.9 to 41.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.58
Confidence Interval (2-Sided) 95%
3.44 to 7.72
Parameter Dispersion
Type: Standard Deviation
Value: 5.35
Estimation Comments Residual standard deviation.
14.Secondary Outcome
Title Short Form 36 - Mental Composite Score
Hide Description The SF-36 is a standard quality of life instrument. The mental composite score represents the the mental burden on quality of life and is a summary of questions related to mental impact of a disease or condition (mental function, role emotional, vitality, and mental health). The score is nomralized to the population and ranges from 0-100, with the US normal value of 50. A lower score represents a greater impact of quality of life.
Time Frame The end of period 1 (week 4) and period 2 (week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intention to treat analysis (n=57). 2 subjects were excluded from analysis due to failure call the IVR system in either period. Treatment group estimates by period are taken from the mixed model, the number above reflecting the number who contributed to the model point estimate. Confidence intervals are bootstrap confidence intervals.
Arm/Group Title Mexiletine - Period 1 Placebo - Period 1 Mexiletine - Period 2 Placebo - Period 2
Hide Arm/Group Description:
SF-36 mental composite for participants receiving mexiletine capsules 200 mg orally three times daily in period 1. Due to an interaction between period and treatment the primary outcome was presented separately for periods 1 and 2.
SF-36 mental composite for participants receiving placebo capsules orally three times daily in period 1. Due to an interaction between period and treatment the primary outcome was presented separately for periods 1 and 2.
SF-36 mental composite for participants receiving mexiletine capsules 200 mg orally three times daily in period 2. Due to an interaction between period and treatment the primary outcome was presented separately for periods 1 and 2.
SF-36 mental composite for participants receiving placebo capsules orally three times daily in period 2. Due to an interaction between period and treatment the primary outcome was presented separately for periods 1 and 2.
Overall Number of Participants Analyzed 28 29 29 25
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
47.4
(44.0 to 50.2)
47.7
(44.2 to 51.3)
53.1
(50.3 to 55.8)
42.7
(36.8 to 48.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine - Period 1, Placebo - Period 1
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. When a carryover effect was detected, the significance level associated with the additive portion of the mexiletine effect (labeled period 1) is followed by the level associated with the interaction of mexiletine and period 2 (labeled period 2). All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.90
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.351
Confidence Interval (2-Sided) 95%
-5.87 to 5.17
Parameter Dispersion
Type: Standard Deviation
Value: 6.50
Estimation Comments Residual standard deviation.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Mexiletine - Period 2, Placebo - Period 2
Comments P value indicates significance level of the Wald test associated with mexiletine effect from the linear mixed effects model. When a carryover effect was detected, the significance level associated with the additive portion of the mexiletine effect (labeled period 1) is followed by the level associated with the interaction of mexiletine and period 2 (labeled period 2). All P values were 2-sided and .05 was considered the threshold of statistical significance.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.4
Confidence Interval (2-Sided) 95%
0.941 to 20.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.50
Estimation Comments Residual standard deviation.
Time Frame Data was collected over a 3 year period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Mexiletine Treatment Placebo Treatment
Hide Arm/Group Description Adverse events that occurred when patients were taking placebo. Adverse events that occurred when patients were taking mexiletine.
All-Cause Mortality
Mexiletine Treatment Placebo Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Mexiletine Treatment Placebo Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/57 (1.75%)      0/57 (0.00%)    
Psychiatric disorders     
Drug withdrawal † 1 [1]  1/1 (100.00%)  1 0/0  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Admitted for withdrawal of narcotics due to pregnancy
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Mexiletine Treatment Placebo Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/57 (42.11%)      11/57 (19.30%)    
Blood and lymphatic system disorders     
Lymphatics † 1  0/57 (0.00%)  0 1/57 (1.75%)  1
Cardiac disorders     
Cardiac † 1  1/57 (1.75%)  1 1/57 (1.75%)  1
Gastrointestinal disorders     
Gastrointestinal † 1  9/57 (15.79%)  9 1/57 (1.75%)  1
General disorders     
Constitutional † 1  3/57 (5.26%)  3 0/57 (0.00%)  0
Pain † 1  4/57 (7.02%)  4 0/57 (0.00%)  0
Infections and infestations     
Infection † 1  1/57 (1.75%)  1 3/57 (5.26%)  3
Musculoskeletal and connective tissue disorders     
Musculosketetal/soft tissue † 1  0/57 (0.00%)  0 2/57 (3.51%)  2
Nervous system disorders     
Neurologic † 1  5/57 (8.77%)  5 1/57 (1.75%)  1
Skin and subcutaneous tissue disorders     
Dermatologic/skin † 1  1/57 (1.75%)  1 2/57 (3.51%)  2
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[Not Specified]
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: Richard J. Barohn, MD
Organization: University of Kansas Medical Center
Phone: 913-588-6095
EMail: rbarohn@kumc.edu
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Richard Barohn, MD, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT00832000    
Obsolete Identifiers: NCT00721942
Other Study ID Numbers: 11050
FDA OPD RO1FD003454
First Submitted: January 27, 2009
First Posted: January 29, 2009
Results First Submitted: October 2, 2012
Results First Posted: March 11, 2013
Last Update Posted: August 23, 2013