Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS)

NCT01849770 | Completed Phase 2 Results DMC

• 1 other identifier: 43708
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this research is to find out if mexiletine is safe and effective in people with Amyotrophic Lateral Sclerosis (ALS). In this trial, participants will be taking either 300 milligrams per day of mexiletine, 900 milligrams per day of mexiletine or placebo (non-active study drug). The safety and efficacy of these doses will be compared to see if one dose is better than the other.

Conditions

Sporadic Amyotrophic Lateral Sclerosis

Keywords

SALS; Mexiletine; Safety

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants That Discontinued Study Drug

  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.

  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 Outcomes (10)

• Trough Plasma Concentration (Cmin) of Mexiletine

  Week 6 Visit (pre-dose, hours 1, 2, 3, and 6 post-dose on Week 6)

• Peak Plasma Concentration (Cmax) of Mexiletine

  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.

  Week 6 Visit (up to 6 hours post dose)

• Mean Cerebrospinal Fluid (CSF)/Plasma Ratio

  Week 6 Visit (up to 6 hours post dose)

• Mean Weekly Cramp Frequency

  Week 3-12, post titration of study medication

Other Outcomes (2)

• Change in ALS Functional Rating Scale- Revised (ALSFRS-R) Score

  Week 0, Week 2, Week 6, Week 12 (or Early Termination Date), and Week 16

• Change in Slow Vital Capacity (SVC) Score

  Week 0, Week 6, and Week 12 (or Early Termination Date)

Study Arms (3)

Mexiletine, 300 milligrams

ACTIVE COMPARATOR

Mexiletine, 300 milligrams by mouth per day for 12 weeks.

Drug: Mexiletine

Mexiletine, 900 milligrams

ACTIVE COMPARATOR

Mexiletine, 900 milligrams by mouth per day for 12 weeks.

Drug: Mexiletine

Placebo

PLACEBO COMPARATOR

Placebo, by mouth per day for 12 weeks.

Drug: Placebo

Interventions

Mexiletine DRUG

Also known as: Mexitil

Mexiletine, 300 milligrams; Mexiletine, 900 milligrams

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Washington: lead

Study Sites (10)

UCLA, Neuromuscular Research Center

Los Angeles, California, 90095, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts (Worcester) Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

SUNY Upstate Medical Center

Syracuse, New York, 13210, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390-8897, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Links

• Northeast ALS Consortium Website

MeSH Terms

Conditions

Amyotrophic lateral sclerosis 1

Interventions

Mexiletine

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenyl Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Michael D. Weiss, MD
• Organization: University of Washington

mdweiss@uw.edu

206-598-7688

Study Officials

• Michael D Weiss, MD

  University of Washington Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Neurology

Study Record Dates

• First Submitted: May 6, 2013
• First Posted: May 8, 2013
• Study Start: July 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 29, 2021
• Results First Posted: October 12, 2015

Record last verified: 2021-09

Locations

US (10)