Myotonia, Non-Dystrophic Myotonia
Conditions
Brief summary
Nondystrophic myotonias (NDM) are neuromuscular disorders caused by genetic abnormalities in certain muscle cell membrane proteins. The proteins affect muscle contraction. Individuals with NDM experience limited muscle relaxation, which then can cause pain, weakness, incoordination, and impaired physical activity and function. Because NDM is very rare, information on the best way to treat people with the disorders is lacking, and there are no FDA-approved therapies. The purpose of this study is to determine the effectiveness of the medication mexiletine in treating people with NDM.
Detailed description
NDM are neuromuscular disorders that are caused by mutations in skeletal muscle ion channels, usually voltage-dependent sodium and chloride channels. The poorly functioning channels result in impaired muscle relaxation after contraction, which is also called myotonia. Mexiletine is an antiarrhythmic medication that has a high affinity for muscle sodium channels and may have the ability to correct delayed inactivation of sodium channels. In case reports and single-blind clinical trials, mexiletine was shown to reduce symptoms of myotonia. Currently, there is no standard strategy for treating people with NDM, and effective treatment options are needed. This study will determine the effectiveness of mexiletine in treating people with NDM. Participation in this study will last 9 weeks and will involve two separate 4-week treatment periods, with a 1-week washout period between them. During the first treatment period, participants will be randomly assigned to receive either mexiletine or placebo, both of which will be taken three times a day. This will be followed by 1 week of no treatment. During the second treatment period, participants will receive whichever treatment they did not receive initially and will follow the same dosing schedule. Participants will attend five study visits that will occur at screening and Weeks 0, 4, 5, and 9. Screening will include blood and urine sampling, electrocardiography (EKG), and a medical history. The remaining visits will include a physical examination, a grip test, exercise tests, nerve conduction tests, blood sampling, questionnaires, and electromyography (EMG). EKG will be repeated at Weeks 4, 5, and 9. Throughout the study, participants will phone in daily to report their symptoms. There will be no follow-up visits. Funded by FDAOPD RO1 0003454.
Interventions
DRUGMexiletine
200 mg three times a day; in pill form
DRUGPlacebo
Placebo three times a day; in pill form
Sponsors
Richard Barohn, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical symptoms or signs suggestive of myotonic disorders * Presence of myotonic potentials on electromyography (EMG) * Participant in the Non-Dystrophic Natural History study (RDCRN 5303) or a new patient with confirmed non-dystrophic myotonia
Exclusion criteria
* Other neurological condition that might affect the assessment of the study measurements * Genetic confirmation of DM1 (more than 50 repeats of CTG) or DM2 * Existing cardiac conduction defects, as evidenced on EKG, including but not limited to the following conditions: malignant arrhythmia or cardiac conduction disturbances (e.g., second degree AV block, third degree AV block, or prolonged QT interval) * Existing permanent pacemaker * Current use of any of the following antiarrhythmic medications for a cardiac disorder: flecainide acetate, encainide, disopyramide, procainamide, quinidine, propafenone, or mexiletine * Use of medications for myotonia, such as phenytoin and flecainide acetate, within 5 days of study entry; carbamazepine and mexiletine within 3 days of study entry; or propafenone, procainamide, disopyramide, quinidine, and encainide within 2 days of study entry * Use of medications that produce myotonia, which may include fibrate acid derivatives, hydroxymethylglutaryl CoA reductase inhibitors, chloroquine, and colchicines * Kidney or liver disease * Heart failure * Seizure disorder * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient-reported Stiffness on the IVR | Weeks 3-4 of each period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Reported Weakness on the IVR | Weeks 3-4 of each period | 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. |
| Patient Reported Tiredness on the IVR | Weeks 3-4 of each period | 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. |
| Quantitative Measure of Hand Grip Myotonia (Seconds) | The end of period 1 (week 4) and period 2 (week 9) | 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. |
| Compound Motor Action Potentials After Short Exercise Test | The end of period 1 (week 4) and period 2 (week 9) | The maximal post-exercise compound muscle action potential (CMAP) after short periods of exercise as a percent of the baseline measurement. |
| Graded Myotonia by Needle Electromyography - Right Abductor Digiti Minimi | The end of period 1 (week 4) and period 2 (week 9) | 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. |
| Clinical Hand Grip Myotonia Evaluation (Seconds) | The end of period 1 (week 4) and the end of period 2 (week 9) | The time to open the fist after a forced handgrip as measured on a stopwatch. |
| Patient Reported Pain on the IVR | Weeeks 3-4 of each period | 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. |
| Graded Myotonia by Needle Electromyography - Right Tibialis Anterior | The end of period 1 (week 4) and period 2 (week 9) | 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. |
| Compound Motor Action Potentials After Long Exercise Test | The end of period 1 (week 4) and period 2 (week 9) | Compound muscle action potential (CMAP) after long periods of exercise as a percentage of baseline. |
| Individualized Neuromuscular Quality of Life Scale - Summary Score | The end of period 1 (week 4) and period 2 (week 9) | 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. |
| Short Form 36 - Physical Composite Score | Particiapnts who experienced weakness on mexiletine in either period 1 or period 2. | 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. |
| Short Form 36 - Mental Composite Score | The end of period 1 (week 4) and period 2 (week 9) | 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. |
| Clinical Eye Closure Myotonia Evaluation (Seconds) | The end of period 1 (week 4) and the end of period 2 (week 9) | Time to open the eyes after forced eye closure as measured on a stopwatch. |
Countries
Canada, Italy, United Kingdom, United States
Participant flow
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).
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants received all inerventions; therefore, we combined all participants into one Arm/Group. | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | No calls to IVR in either period | 1 | 1 |
| Overall Study | No calls to IVR in period 2 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 56 Participants |
| Age Continuous | 42.9 years STANDARD_DEVIATION 25 |
| Region of Enrollment Canada | 4 participants |
| Region of Enrollment Italy | 12 participants |
| Region of Enrollment United Kingdom | 12 participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 57 | 11 / 57 |
| serious Total, serious adverse events | 1 / 57 | 0 / 57 |
Outcome results
Primary
Patient-reported Stiffness on the IVR
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
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Patient-reported Stiffness on the IVR | 2.53 units on a scale |
| Placebo - Period 1 | Patient-reported Stiffness on the IVR | 4.21 units on a scale |
| Mexiletine - Period 2 | Patient-reported Stiffness on the IVR | 1.60 units on a scale |
| Placebo - Period 2 | Patient-reported Stiffness on the IVR | 5.27 units on a scale |
Comparison: 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.p-value: <0.00195% CI: [-2.66, -0.706]Wald
Comparison: 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.p-value: 0.0495% CI: [-3.85, -0.139]Wald
Secondary
Clinical Eye Closure Myotonia Evaluation (Seconds)
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Clinical Eye Closure Myotonia Evaluation (Seconds) | 0.161 Seconds |
| Placebo - Period 1 | Clinical Eye Closure Myotonia Evaluation (Seconds) | 0.474 Seconds |
Comparison: 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.p-value: <0.00195% CI: [-0.602, -0.149]Wald
Secondary
Clinical Hand Grip Myotonia Evaluation (Seconds)
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Clinical Hand Grip Myotonia Evaluation (Seconds) | 0.164 Seconds |
| Placebo - Period 1 | Clinical Hand Grip Myotonia Evaluation (Seconds) | 0.494 Seconds |
Comparison: 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.p-value: <0.00195% CI: [-0.633, -0.142]Wald
Secondary
Compound Motor Action Potentials After Long Exercise Test
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Compound Motor Action Potentials After Long Exercise Test | 81.8 percentage of baseline CMAP amplitude |
| Placebo - Period 1 | Compound Motor Action Potentials After Long Exercise Test | 80.1 percentage of baseline CMAP amplitude |
Comparison: 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.p-value: 0.595% CI: [-3.34, 6.73]wald
Secondary
Compound Motor Action Potentials After Short Exercise Test
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Compound Motor Action Potentials After Short Exercise Test | 83.1 percentage of baseline CMAP amplitude |
| Placebo - Period 1 | Compound Motor Action Potentials After Short Exercise Test | 78.6 percentage of baseline CMAP amplitude |
Comparison: 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.p-value: 0.0995% CI: [-0.68, 9.75]wald
Secondary
Graded Myotonia by Needle Electromyography - Right Abductor Digiti Minimi
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Graded Myotonia by Needle Electromyography - Right Abductor Digiti Minimi | 2.05 units on a scale |
| Placebo - Period 1 | Graded Myotonia by Needle Electromyography - Right Abductor Digiti Minimi | 2.62 units on a scale |
Comparison: 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.p-value: <0.00195% CI: [-0.812, -0.325]Wilcoxon (Mann-Whitney)
Secondary
Graded Myotonia by Needle Electromyography - Right Tibialis Anterior
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Graded Myotonia by Needle Electromyography - Right Tibialis Anterior | 2.07 units on a scale |
| Placebo - Period 1 | Graded Myotonia by Needle Electromyography - Right Tibialis Anterior | 2.54 units on a scale |
Comparison: 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.p-value: <0.00195% CI: [-0.675, -0.254]Wilcoxon (Mann-Whitney)
Secondary
Individualized Neuromuscular Quality of Life Scale - Summary Score
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Individualized Neuromuscular Quality of Life Scale - Summary Score | 14.0 units on a scale |
| Placebo - Period 1 | Individualized Neuromuscular Quality of Life Scale - Summary Score | 16.7 units on a scale |
Comparison: 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.p-value: <0.00195% CI: [-4.07, -1.3]wald
Secondary
Patient Reported Pain on the IVR
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
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Patient Reported Pain on the IVR | 1.54 units on a scale |
| Placebo - Period 1 | Patient Reported Pain on the IVR | 3.17 units on a scale |
Comparison: 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.p-value: <0.00195% CI: [-2, -1.26]Wald
Secondary
Patient Reported Tiredness on the IVR
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
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Patient Reported Tiredness on the IVR | 2.90 units on a scale |
| Placebo - Period 1 | Patient Reported Tiredness on the IVR | 3.82 units on a scale |
Comparison: 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.p-value: <0.00195% CI: [-1.3, -0.532]Wald
Secondary
Patient Reported Weakness on the IVR
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
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Patient Reported Weakness on the IVR | 1.96 units on a scale |
| Placebo - Period 1 | Patient Reported Weakness on the IVR | 3.22 units on a scale |
Comparison: 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.p-value: <0.00195% CI: [-1.67, -0.861]Wald
Secondary
Quantitative Measure of Hand Grip Myotonia (Seconds)
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Quantitative Measure of Hand Grip Myotonia (Seconds) | 0.321 seconds |
| Placebo - Period 1 | Quantitative Measure of Hand Grip Myotonia (Seconds) | 0.429 seconds |
Comparison: 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.p-value: <0.00195% CI: [-0.177, -0.056]Wald
Secondary
Short Form 36 - Mental Composite Score
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Short Form 36 - Mental Composite Score | 47.4 units on a scale |
| Placebo - Period 1 | Short Form 36 - Mental Composite Score | 47.7 units on a scale |
| Mexiletine - Period 2 | Short Form 36 - Mental Composite Score | 53.1 units on a scale |
| Placebo - Period 2 | Short Form 36 - Mental Composite Score | 42.7 units on a scale |
Comparison: 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.p-value: 0.995% CI: [-5.87, 5.17]Wald
Comparison: 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.p-value: 0.0395% CI: [0.941, 20.6]wald
Secondary
Short Form 36 - Physical Composite Score
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.
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Mexiletine - Period 1 | Short Form 36 - Physical Composite Score | 44.8 units on a scale |
| Placebo - Period 1 | Short Form 36 - Physical Composite Score | 39.2 units on a scale |
Comparison: 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.p-value: <0.00195% CI: [3.44, 7.72]wald