Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS) (MX-ALS-001)

• ClinicalTrials.gov Identifier: NCT01849770
• Recruitment Status: Completed
• First Posted: May 8, 2013
• Results First Posted: October 12, 2015
• Last Update Posted: September 29, 2021
• Sponsor: University of Washington
• 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: 75

Participant Flow

Recruitment Details	The first subject in the study was enrolled July 23, 2013. Subjects were recruited and seen at Amyotrophic Lateral Sclerosis (ALS) clinics at 10 sites across the United States (U.S.).
Pre-assignment Details	Seventy-five (75) subjects signed the consent form and were considered enrolled in the study. Fifteen (15) subjects did not meet eligibility criteria and were considered screen failures. Sixty (60) subjects were randomized to one of three treatment arms. One (1) subject was randomized to the 900mg group but never started study drug.

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Period Title: Overall Study
Started	20	19	20
Completed	20	15	19
Not Completed	0	4	1

Baseline Characteristics

Arm/Group Title		Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo	Total
Arm/Group Description		Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo	Total of all reporting groups
Overall Number of Baseline Participants		20	19	20	59
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		59.2 (7.1)	58.0 (10.7)	57.0 (7.0)	58.0 (8.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
	Female	6 30.0%	7 36.8%	10 50.0%	23 39.0%
	Male	14 70.0%	12 63.2%	10 50.0%	36 61.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	20 participants	19 participants	20 participants	59 participants
Asian		1	0	0	1
Caucasian		19	19	20	58
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		20	19	20	59
Months Since Symptom Onset [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		21.0 (10.3)	18.6 (9.2)	17.5 (8.3)	19.0 (9.3)
		[1] Measure Description: Number of months since ALS symptom onset prior to enrolling into this study.
Months Since Diagnosis [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		8.6 (7.7)	8.9 (8.2)	7.3 (5.9)	8.3 (7.2)
		[1] Measure Description: Number of months since enrolling into the study that a subject was diagnosed with ALS.
Slow Vital Capacity (Max % predicted); Mean (Standard Deviation); Unit of measure: Max %-predicted
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		86.7 (19.1)	86.2 (23.7)	83.7 (22.6)	85.6 (21.5)
Body Mass Index (BMI) (kg/m^2); Mean (Standard Deviation); Unit of measure: Kilograms (kg)/meter squared (m^2)
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		28.1 (5.1)	27.3 (4.1)	27.1 (3.3)	27.5 (4.2)
Baseline Cramps in Previous 24 hours; Mean (Standard Deviation); Unit of measure: Number of Cramps
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		1.97 (3.06)	1.68 (1.63)	2.15 (2.13)	1.94 (2.31)
Baseline Cramps in Previous 30 Days; Mean (Standard Deviation); Unit of measure: Number of Cramps
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		52.9 (91.0)	29.1 (43.9)	46.2 (55.9)	42.8 (66.1)
Maximum Cramp Pain in Previous 24 hours [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		1.75 (2.24)	2.32 (2.11)	2.55 (2.78)	2.20 (2.38)
		[1] Measure Description: Cramp pain measured at 0 no pain and 10 is worst pain.
Maximum Cramp Pain in Previous 30 Days [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		3.00 (2.38)	3.37 (2.36)	3.35 (2.70)	3.24 (2.45)
		[1] Measure Description: Cramp pain measured at 0 no pain and 10 is worst pain.
ALSFRS-R Total Score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		36.3 (7.8)	33.6 (6.7)	34.9 (5.5)	35.0 (6.7)
		[1] Measure Description: ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score at Baseline. Scale is measured from 0 (worst score) to 48 points (best score).

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants That Discontinued Study Drug
Description	Information on adverse effects of mexiletine will be determined at each visit by direct questioning of the subjects, clinical examination, review of concomitant medications, vital signs and laboratory test results.
Time Frame	Screening, Baseline Visit Pre-Dose and Post-Dose, Weeks 2, 6, and 12, and at the Final Safety Visit, if a subject discontinues study drug early. Adverse Events will be assessed via telephone Weeks 1, 10, and 16.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Measure Type: Number; Unit of Measure: percentage of participants
	5	32	5

2. Secondary Outcome

Title	Trough Plasma Concentration (Cmin) of Mexiletine
Description	Subjects will have blood drawn to assess mexiletine concentrations for pharmacokinetics (PK) at the Week 6 Visit.
Time Frame	Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (Standard Deviation); Unit of Measure: pg/mL
	0.23 (0.15)	0.68 (0.38)	0 (0)

3. Secondary Outcome

Title	Peak Plasma Concentration (Cmax) of Mexiletine
Description	Subjects will have blood drawn to assess mexiletine concentrations for pharmacokinetics (PK) at the Week 6 Visit.
Time Frame	Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (Standard Deviation); Unit of Measure: pg/mL
	0.41 (0.19)	1.27 (0.67)	0 (0)

4. Secondary Outcome

Title	Area Under the Concentration Time Curve (AUC) of Mexiletine in Plasma.
Description	Subjects will have blood drawn to assess mexiletine concentrations for pharmacokinetics (PK) at the Week 6 Visit.
Time Frame	Week 6 Visit (up to 6 hours post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (Standard Deviation); Unit of Measure: µg*hr/mL
	2.34 (1.08)	6.24 (3.18)	0 (0)

5. Secondary Outcome

Title	Mean Cerebrospinal Fluid (CSF)/Plasma Ratio
Description	The concentrations of Mexiletine were measured in cerebrospinal fluid (CSF) and plasma.
Time Frame	Week 6 Visit (up to 6 hours post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (Standard Deviation); Unit of Measure: ratio
	0.38 (0.15)	0.46 (0.20)	0 (0)

6. Secondary Outcome

Title	Mean Weekly Cramp Frequency
Description	[Not Specified]
Time Frame	Week 3-12, post titration of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (95% Confidence Interval); Unit of Measure: cramps/week
All Subjects n=20,19,20	0.785; (0.304 to 2.023)	0.231; (0.125 to 1.250)	2.505; (1.030 to 6.092)
10+cramps previous 30 days at Baseline n=20,19,20	1.898; (0.494 to 7.288)	0.595; (0.112 to 3.153)	8.563; (3.217 to 22.79)

7. Secondary Outcome

Title	Maximal Pain Severity
Description	At the Baseline Visit, subjects will be asked to recount the maximum intensity experienced with a muscle cramp in the previous 24 hours and the maximum intensity experienced with a muscle cramp in the previous 30 days. The visual analog scale (VAS) will be used to measures pain associated with muscle cramping. It will be used to measure muscle cramp intensity in this study. The scale rating is from 0-10; 0 equals no symptoms, 10 equals most severe symptoms. Subject will be provided with a muscle cramp diary to record muscle cramp intensity at home, daily.
Time Frame	Weeks 3-12, post titration of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (95% Confidence Interval); Unit of Measure: units on a scale
All Subjects n=20,19,20	0.738; (0.364 to 1.494)	0.340; (0.117 to 0.986)	0.939; (0.466 to 1.893)
10+cramps previous 30 days at Baseline n=20,19,20	1.348; (0.616 to 2.953)	0.572; (0.176 to 1.859)	2.033; (1.123 to 3.681)

8. Secondary Outcome

Title	Cramp Frequency - Ratios for Comparisons of Doses for Weeks 3-12
Description	[Not Specified]
Time Frame	Week 3-12, post titration of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	300mg vs Placebo	900mg vs Placebo
Arm/Group Description:	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	20	19
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: ratio
All Subjects n=20,19	0.313; (0.100 to 0.982)	0.158; (0.050 to 0.495)
10+cramps previous 30 days at Baseline n=20,19	0.222; (0.079 to 0.624)	0.069; (0.013 to 0.374)

9. Secondary Outcome

Title	Maximal Pain Severity - Ratios for Comparisons of Doses for Weeks 3-12
Description	[Not Specified]
Time Frame	Week 3-12, post titration of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	300mg vs Placebo	900mg vs Placebo
Arm/Group Description:	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	20	19
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: ratio
All Subjects n=20,19	0.785; (0.342 to 1.802)	0.361; (0.131 to 1.000)
10+cramps previous 30 days at Baseline n=20,19	0.663; (0.347 to 1.267)	0.281; (0.080 to 0.992)

10. Secondary Outcome

Title	Mean Pain Severity
Description	At the Baseline Visit, subjects will be asked to recount the maximum intensity experienced with a muscle cramp in the previous 24 hours and the maximum intensity experienced with a muscle cramp in the previous 30 days. The visual analog scale (VAS) will be used to measures pain associated with muscle cramping. It will be used to measure muscle cramp intensity in this study. The scale rating is from 0-10; 0 equals no symptoms, 10 equals most severe symptoms. Subject will be provided with a muscle cramp diary to record muscle cramp intensity at home, daily.
Time Frame	Weeks 3-12, post titration of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (95% Confidence Interval); Unit of Measure: units on a scale
All Subjects n=20,19,20	0.241; (0.115 to 0.509)	0.136; (0.049 to 0.379)	0.536; (0.275 to 1.046)
10+cramps previous 30 days at Baseline n=20,19,20	0.467; (0.145 to 1.504)	0.201; (0.050 to 0.812)	1.248; (0.527 to 2.958)

11. Secondary Outcome

Title	Mean Pain Severity - Ratios for Comparisons of Doses for Weeks 3-12
Description	[Not Specified]
Time Frame	Week 3-12, post titration of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	300mg vs Placebo	900mg vs Placebo
Arm/Group Description:	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	20	19
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: ratio
All Subjects n=20,19	0.450; (0.183 to 1.110)	0.254; (0.098 to 0.658)
10+cramps previous 30 days at Baseline n=20,19	0.374; (0.135 to 1.035)	0.161; (0.032 to 0.795)

12. Other Pre-specified Outcome

Title	Change in ALS Functional Rating Scale- Revised (ALSFRS-R) Score
Description	The ALSFRS-R is a quickly administered (5 minutes) ordinal rating scale (ratings 0-4) used to determine subjects' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, was closely associated with quality of life measures, and predicted survival.
Time Frame	Week 0, Week 2, Week 6, Week 12 (or Early Termination Date), and Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (95% Confidence Interval); Unit of Measure: scores on a scale
Week 0 n=20,19,20	35.21; (32.9 to 37.5)	35.21; (32.9 to 37.5)	35.21; (32.9 to 37.5)
Week 2 n=20,19,20	35.14; (32.7 to 37.6)	34.58; (32.0 to 37.1)	35.47; (33.0 to 37.9)
Week 6 n=20,19,20	35.72; (33.1 to 38.3)	33.08; (30.4 to 35.8)	34.25; (31.7 to 36.8)
Week 12 n=20,19,20	33.33; (30.4 to 36.3)	31.85; (28.6 to 35.1)	33.48; (30.5 to 36.4)
Week 16 n=20,19,20	32.44; (29.2 to 35.7)	31.94; (28.2 to 35.6)	32.96; (29.7 to 36.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mexiletine, 300 Milligrams, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.561
	Comments	[Not Specified]
	Method	Random slopes model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -1.03 to 0.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.40
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mexiletine, 900 Milligrams, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.662
	Comments	[Not Specified]
	Method	Random slopes model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -1.04 to 0.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.43
	Estimation Comments	[Not Specified]

13. Other Pre-specified Outcome

Title	Change in Slow Vital Capacity (SVC) Score
Description	The vital capacity (VC) (percent of predicted normal) will be determined, using the slow VC method. The SVC can be measured using conventional spirometers that have had a calibration check prior to subject testing. A printout from the spirometer of all SVC trials will be retained.
Time Frame	Week 0, Week 6, and Week 12 (or Early Termination Date)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mexiletine, 300 Milligrams	Mexiletine, 900 Milligrams	Placebo
Arm/Group Description:	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine	Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine	Placebo, by mouth per day for 12 weeks. Placebo
Overall Number of Participants Analyzed	20	19	20
Mean (95% Confidence Interval); Unit of Measure: percent of predicted normal
Week 0 n=20,19,20	87.74; (80.0 to 95.5)	87.74; (80.0 to 95.5)	87.74; (80.0 to 95.5)
Week 6 n=20,19,20	86.51; (78.1 to 94.9)	82.92; (73.9 to 91.9)	84.79; (76.3 to 93.3)
Week 12 n=20,19,20	83.98; (75.1 to 92.8)	77.18; (67.0 to 87.4)	79.58; (70.7 to 88.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mexiletine, 300 Milligrams, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.178
	Comments	[Not Specified]
	Method	Random slopes model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; -0.80 to 4.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.25
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mexiletine, 900 Milligrams, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.510
	Comments	[Not Specified]
	Method	Random slopes model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.94
	Confidence Interval	(2-Sided) 95%; -3.80 to 1.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.42
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Mexiletine, 300 Milligrams		Mexiletine, 900 Milligrams		Placebo
Arm/Group Description	Mexiletine, 300 milligrams by mouth per day for 12 weeks. Mexiletine		Mexiletine, 900 milligrams by mouth per day for 12 weeks. Mexiletine		Placebo, by mouth per day for 12 weeks. Placebo
All-Cause Mortality
	Mexiletine, 300 Milligrams		Mexiletine, 900 Milligrams		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Mexiletine, 300 Milligrams		Mexiletine, 900 Milligrams		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0.00%)		1/19 (5.26%)		2/20 (10.00%)
Injury, poisoning and procedural complications
Lower Limb Fracture *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Nervous system disorders
Balance Disorder *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Respiratory Failure *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Mexiletine, 300 Milligrams		Mexiletine, 900 Milligrams		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/20 (85.00%)		19/19 (100.00%)		18/20 (90.00%)
Ear and labyrinth disorders
Tinnitus *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Gastrointestinal disorders
Abdominal Discomfort *	1/20 (5.00%)	1	2/19 (10.53%)	2	0/20 (0.00%)	0
Abdominal Distension *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Abdominal Pain *	0/20 (0.00%)	0	0/19 (0.00%)	0	3/20 (15.00%)	4
Constipation *	1/20 (5.00%)	1	4/19 (21.05%)	4	2/20 (10.00%)	2
Dry Mouth *	1/20 (5.00%)	1	1/19 (5.26%)	1	1/20 (5.00%)	1
Dyspepsia *	1/20 (5.00%)	1	1/19 (5.26%)	1	3/20 (15.00%)	3
Dysphagia *	1/20 (5.00%)	1	1/19 (5.26%)	1	0/20 (0.00%)	0
Eructation *	1/20 (5.00%)	1	1/19 (5.26%)	1	0/20 (0.00%)	0
Gastroesophageal Reflux Disease *	0/20 (0.00%)	0	1/19 (5.26%)	2	0/20 (0.00%)	0
Haemorrhoids *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Hypoaesthesia Oral *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Nausea *	1/20 (5.00%)	1	8/19 (42.11%)	15	2/20 (10.00%)	2
Salivary Hypersecretion *	1/20 (5.00%)	1	1/19 (5.26%)	1	0/20 (0.00%)	0
Toothache *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Vomiting *	1/20 (5.00%)	1	2/19 (10.53%)	6	0/20 (0.00%)	0
General disorders
Asthenia *	1/20 (5.00%)	1	3/19 (15.79%)	4	2/20 (10.00%)	2
Chest Discomfort *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Drug Withdrawal Syndrome *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Fatigue *	2/20 (10.00%)	4	4/19 (21.05%)	7	3/20 (15.00%)	3
Feeling Jittery *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Gait Disturbance *	1/20 (5.00%)	2	0/19 (0.00%)	0	1/20 (5.00%)	1
Oedema Peripheral *	1/20 (5.00%)	2	0/19 (0.00%)	0	1/20 (5.00%)	1
Pain *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Infections and infestations
Cystitis *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Ear Infection *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Gastroenteritis *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Herpes Zoster *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Influenza *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Nasopharyngitis *	1/20 (5.00%)	1	0/19 (0.00%)	0	1/20 (5.00%)	1
Oral Herpes *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Upper Respiratory Tract Infection *	2/20 (10.00%)	2	1/19 (5.26%)	1	2/20 (10.00%)	2
Urinary Tract Infection *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Injury, poisoning and procedural complications
Contusion *	2/20 (10.00%)	3	0/19 (0.00%)	0	1/20 (5.00%)	2
Excoriation *	1/20 (5.00%)	1	0/19 (0.00%)	0	1/20 (5.00%)	2
Fall *	2/20 (10.00%)	2	5/19 (26.32%)	6	4/20 (20.00%)	7
Joint Sprain *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Lower Limb Fracture *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Post Lumbar Puncture Syndrome *	2/20 (10.00%)	2	5/19 (26.32%)	5	2/20 (10.00%)	2
Post Procedural Discomfort *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Procedural Nausea *	1/20 (5.00%)	1	1/19 (5.26%)	1	0/20 (0.00%)	0
Procedural Pain *	1/20 (5.00%)	1	4/19 (21.05%)	5	2/20 (10.00%)	2
Skin Laceration *	0/20 (0.00%)	0	2/19 (10.53%)	2	0/20 (0.00%)	0
Investigations
Blood Glucose Increased *	0/20 (0.00%)	0	2/19 (10.53%)	2	0/20 (0.00%)	0
Blood Potassium Decreased *	1/20 (5.00%)	1	1/19 (5.26%)	1	0/20 (0.00%)	0
Blood Pressure Diastolic Decreased *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Heart Rate Irregular *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Urine Analysis Abnormal *	1/20 (5.00%)	1	1/19 (5.26%)	1	0/20 (0.00%)	0
Urine Output Increased *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Weight Decreased *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Metabolism and nutrition disorders
Decreased Appetite *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia *	0/20 (0.00%)	0	0/19 (0.00%)	0	2/20 (10.00%)	2
Back Pain *	2/20 (10.00%)	2	0/19 (0.00%)	0	2/20 (10.00%)	2
Joint Swelling *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Muscle Spasms *	1/20 (5.00%)	1	3/19 (15.79%)	3	2/20 (10.00%)	3
Muscle Tightness *	1/20 (5.00%)	1	1/19 (5.26%)	1	0/20 (0.00%)	0
Muscular Weakness *	3/20 (15.00%)	5	3/19 (15.79%)	3	3/20 (15.00%)	3
Musculoskeletal Stiffness *	2/20 (10.00%)	2	1/19 (5.26%)	1	0/20 (0.00%)	0
Myalgia *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Neck Pain *	1/20 (5.00%)	1	0/19 (0.00%)	0	1/20 (5.00%)	2
Pain in Extremity *	0/20 (0.00%)	0	3/19 (15.79%)	3	0/20 (0.00%)	0
Sensation of Heaviness *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Nervous system disorders
Balance Disorder *	0/20 (0.00%)	0	2/19 (10.53%)	2	1/20 (5.00%)	1
Crying *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Dizziness *	3/20 (15.00%)	4	6/19 (31.58%)	7	4/20 (20.00%)	4
Dysarthria *	0/20 (0.00%)	0	2/19 (10.53%)	2	0/20 (0.00%)	0
Dysgeusia *	0/20 (0.00%)	0	2/19 (10.53%)	2	0/20 (0.00%)	0
Headache *	2/20 (10.00%)	2	4/19 (21.05%)	6	2/20 (10.00%)	3
Hypoaesthesia *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Memory Impairment *	0/20 (0.00%)	0	1/19 (5.26%)	1	1/20 (5.00%)	1
Muscle Contractions Involuntary *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Neuralgia *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Paraesthesia *	0/20 (0.00%)	0	0/19 (0.00%)	0	2/20 (10.00%)	2
Tremor *	0/20 (0.00%)	0	5/19 (26.32%)	7	1/20 (5.00%)	1
Psychiatric disorders
Affect Lability *	0/20 (0.00%)	0	3/19 (15.79%)	3	0/20 (0.00%)	0
Anxiety *	1/20 (5.00%)	1	3/19 (15.79%)	3	0/20 (0.00%)	0
Depression *	0/20 (0.00%)	0	2/19 (10.53%)	3	2/20 (10.00%)	2
Euphoric Mood *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Insomnia *	0/20 (0.00%)	0	1/19 (5.26%)	1	1/20 (5.00%)	1
Nervousness *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Renal and urinary disorders
Chromaturia *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Pollakiuria *	1/20 (5.00%)	1	1/19 (5.26%)	1	0/20 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Choking *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Cough *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Dyspnoea *	1/20 (5.00%)	1	1/19 (5.26%)	1	3/20 (15.00%)	4
Epistaxis *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Productive Cough *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Respiratory Failure *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Rhinorrhoea *	0/20 (0.00%)	0	1/19 (5.26%)	1	1/20 (5.00%)	1
Throat Irritation *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Skin and subcutaneous tissue disorders
Heat Rash *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Night Sweats *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Pruritus *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Skin Disorder *	1/20 (5.00%)	1	0/19 (0.00%)	0	0/20 (0.00%)	0
Rash Pruritic *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
Surgical and medical procedures
Epidural Blood Patch *	0/20 (0.00%)	0	2/19 (10.53%)	2	0/20 (0.00%)	0
Surgical Stapling *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Vascular disorders
Flushing *	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
Haematoma *	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	2
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Michael D. Weiss, MD
• Organization: University of Washington
• Phone: 206-598-7688
• EMail: mdweiss@uw.edu

• Responsible Party: Michael D Weiss, University of Washington
• ClinicalTrials.gov Identifier: NCT01849770
• Other Study ID Numbers: 43708
• First Submitted: May 6, 2013
• First Posted: May 8, 2013
• Results First Submitted: July 7, 2015
• Results First Posted: October 12, 2015
• Last Update Posted: September 29, 2021