A Safety & Tolerability Study of Mexiletine in Patients with Sporadic Amyotrophc Lateral Sclerosis (ALS)

Study ID
STU 102012-010

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Nina Gorham
214-648-0462
nina.gorham@utsouthwestern.edu

Principal Investigator
Jaya Trivedi

Summary

This is a randomized, double-blind, placebo-controlled study evaluating the safety and tolerability of oral administration of mexiletine 300 mg/day or 900 mg/day) or placebo for 12 weeks in a Phase ii multicenter study of subjects with sporadic aLS with more limited evaluation of the efficacy of the study drug with regard to slowing progression.
During the enrollment period 60 subjects recruited from approximately 10 northeast aLS Consortium (neaLS) centers in the uS will be randomized in a 1:1:1 ratio to one of three groups: placebo or mexiletine 300mg/day or mexiletine 900 mg/day. after screening and randomization, participants will be followed at Week 1 Telephone Call, Week 2, Week 6, Week 10 Telephone Call and Week 12 Visits. There will be a 28-day (+5 days) post-treatment, Week 16 Follow-up Telephone interview to assess medical status and adverse events.
all visit windows are consecutive calendar days and are calculated from the day the participant starts study medication (the day of the Baseline Visit).

Variables
The safety of mexiletine will be evaluated using vital signs, weight, clinical laboratory determinations, physical examinations, aes (including deaths and other Saes), use of concomitant medications and treatment discontinuations (tolerability).

outcome Measures
aLSFRS-R,Slow Vital Capacity (Pulmonary Function Testing/Spirometry),

Participant Eligibility

1. Sporadic ALS diagnosed as possible, laboratory-supported probable, probable, or definite ALS as defined by revised El Escorial criteria.
2. Age 18 years or older.
3.Disease duration <= 36 months from ALS symptom onset.
4.Capable of providing informed consent and following trial procedures.
5.Subjects must not have taken riluzole for at least 30 days or be on a 50 mg BID dose of riluzole for at least 60 days prior to randomization (riluzole-naive subjects are permitted in the study).
6.Geographic accessibility to the site.
7.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.
8.Slow vital capacity (SVC) measure >=50% of predicted for gender, height, and age at the screening visit.
9.Must be able to swallow capsules throughout the course of the study, according to PI judgment.
10.Must have a caregiver assist with dispensing the study drug.
11. Subjects must not have taken medication for muscle cramping such as cyclobenzaprine, baclofen, carisoprodol, or methacarbamol, for at least 30 days prior to randomization or be on a stable dose for at least 60 days prior to randomization.
12. Subjects medically able to undergo lumbar puncture (LP) as determined by the investigator (i.e. no bleeding disorder, allergy to local anesthetics, a skin infection at or near the LP site, or evidence of high intracranial pressure).