Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS)

• Register: ClinicalTrials.gov
• Last refreshed on: 11 October 2021
• Main ID: NCT01849770
• Date of registration: 06/05/2013
• Prospective Registration: Yes
• Primary sponsor: University of Washington
• Public title: Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS) MX-ALS-001
• Scientific title: A Safety and Tolerability Study of Mexiletine in Patients With Sporadic Amyotrophic Lateral Sclerosis (SALS)
• Date of first enrolment: July 2013
• Target sample size: 75
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01849770
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Michael D Weiss, MD
• Affiliation: University of Washington Medical School

Key inclusion & exclusion criteria

Inclusion Criteria:

- Sporadic Amyotrophic Lateral Sclerosis (SALS) diagnosed as possible,
laboratory-supported probable, probable, or definite ALS as defined by revised El
Escorial criteria.

- Age 18 years or older.

- Disease duration = 36 months from ALS symptom onset.

- Capable of providing informed consent and following trial procedures.

- Subjects must not have taken riluzole for at least 30 days or be on a 50 milligrams
twice daily dose of riluzole for at least 60 days prior to randomization
(riluzole-naïve subjects are permitted in the study).

- Subjects must not have taken medication for muscle cramping such as cyclobenzaprine,
baclofen, carisoprodol, or methocarbamol, for at least 30 days prior to randomization
or be on a stable dose for at least 60 days prior to randomization.

- Geographic accessibility to the site.

- Women must not become pregnant for the duration of the study and must be willing to
use two contraceptive therapies and have a negative pregnancy test throughout the
course of the study.

- Slow vital capacity (SVC) measure greater than or equal to 50% of predicted for
gender, height, and age at the screening visit.

- Subjects medically able to undergo lumbar puncture (LP) as determined by the
investigator (for example, no bleeding disorder, allergy to local anesthetics, a skin
infection at or near the LP site, or evidence of high intracranial pressure).

- Must be able to swallow capsules throughout the course of the study, according to
Principal Investigator (PI) judgment.

- Must have a caregiver assist with dispensing the study drug.

Exclusion Criteria:

- Invasive ventilator dependence, such as tracheostomy.

- Creatinine level greater than 1.5 milligram/deciliter.

- Serum glutamic oxaloacetic transaminase or (aspartate transaminase) / serum glutamic
pyruvic transaminase (alanine aminotransferase) greater than 3 times the upper limit
of normal at screening.

- History of known sensitivity or intolerability to mexiletine or lidocaine.

- Any history of either substance abuse within the past year, unstable psychiatric
disease, cognitive impairment, or dementia.

- Clinically significant conduction abnormalities on electrocardiogram or a known
history of cardiac arrhythmia.

- Known history of epilepsy.

- Known history of congestive heart failure (CHF) or history of myocardial infarction
within the past 24 months.

- Use of mexiletine for 60 days prior to Baseline Visit.

- Exposure to any other experimental agent (off-label use or investigational) including
high dose creatine (greater than 10 grams a day) within 30 days prior to Baseline
Visit.

- Use of amiodarone, flecainide, duloxetine, tizanidine, or clozapine.

- Pregnant women or women currently breastfeeding.

- Placement of Diaphragm Pacing System (DPS) device less than 60 days prior to Baseline
Visit.

- Planned DPS device implantation after Baseline Visit.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Sporadic Amyotrophic Lateral Sclerosis

Intervention(s)

Drug: Mexiletine

Drug: Placebo

Primary Outcome(s)

Percentage of Participants That Discontinued Study Drug [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.]

Secondary Outcome(s)

Mean Pain Severity [Time Frame: Weeks 3-12, post titration of study medication]

Trough Plasma Concentration (Cmin) of Mexiletine [Time Frame: Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)]

Area Under the Concentration Time Curve (AUC) of Mexiletine in Plasma. [Time Frame: Week 6 Visit (up to 6 hours post dose)]

Cramp Frequency - Ratios for Comparisons of Doses for Weeks 3-12 [Time Frame: Week 3-12, post titration of study medication]

Mean Cerebrospinal Fluid (CSF)/Plasma Ratio [Time Frame: Week 6 Visit (up to 6 hours post dose)]

Mean Pain Severity - Ratios for Comparisons of Doses for Weeks 3-12 [Time Frame: Week 3-12, post titration of study medication]

Maximal Pain Severity - Ratios for Comparisons of Doses for Weeks 3-12 [Time Frame: Week 3-12, post titration of study medication]

Maximal Pain Severity [Time Frame: Weeks 3-12, post titration of study medication]

Peak Plasma Concentration (Cmax) of Mexiletine [Time Frame: Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)]

Mean Weekly Cramp Frequency [Time Frame: Week 3-12, post titration of study medication]

Secondary ID(s)

43708

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/10/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01849770