Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1

During this assessment, participants were asked to walk as far as they could back and forth on a fixed 20 meter route for 6 minutes. The total distance walked during the 6 minutes was recorded in meters. Change from baseline was defined as the difference between the average 6 minute walk distance at baseline and the average 6 minute walk distance at 6 months.

Time frame: Baseline to 6 months

Population: Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment. Follow-up data was not collected on one participant in the mexiletine arm due to a broken foot.

Manual muscle testing was performed on 26 muscle groups (shoulder abductors, elbow flexors, wrist flexors, wrist extensors, hip flexors, knee extensors, hip extensors, knee flexors, hip abductors, elbow extensors, ankle dorsiflexors, and plantar flexors on the right and left plus neck extensor and neck flexors). The muscles were tested in various positions including sitting, supine, prone, and side lying and each graded on a modification of the Medical Research Council (MRC) scale of 0 to 5 (5 representing normal strength). Average MMT score is derived by averaging the individual MMT scores across the 26 individual muscles.

Time frame: Baseline to 6 months

Population: Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment.

* The Myotonic Dystrophy Health Index (MDHI) is a validated disease-specific measure of patient-reported disease burden. The MDHI total score is a weighted average derived from 17 subscales. MDHI total scores range form 0-100 with 0 representing no patient-reported disease burden and 100 representing the most severe patient-reported disease burden. * The Individualized Neuromuscular Quality of Life Questionnaire (INQoL) is a measure of quality of life in neuromuscular disease. The INQoL summary score is a weighted average made up of 5 sub-domains. Scores range from 0-100, and can be interpreted as the percent of maximal detrimental impact on quality of life with higher scores indicating more detrimental impact. * The 36-Item Short Form Survey (SF-36) is a generic measure of quality of life across 8 domains. Two summary metrics are produced from the 8 domains, ranging from 0-100% with lower scores representing worse levels of functioning.

Time frame: Baseline to 6 months

Population: Intent to treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment.

PR, QRS, and QTc intervals as well as average minimum heart rate (HR) were obtained through standard 12 lead electrocardiograms (ECGs). Values were computer generated and verified by the study investigator and study cardiologist.

Time frame: Baseline to 6 Months

Population: Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment.

Relaxation time of the long finger flexor muscles of the right hand after a maximum voluntary isometric contraction performed in a standardized fixed position of the right arm elbow/wrist/hand. Relaxation time for this measurement is defined as the time to relax from 90% to 5% of the maximum isometric force of contraction of the hand (the first of 6 serial contractions averaged over two consecutive trials performed 10 minutes apart).

Time frame: Baseline to 6 months

Population: Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication, and have post-baseline efficacy assessment at 6 months. Data was not analyzable on 3 people in the placebo arm.

Adverse events were monitored at the three in-person evaluations (Months 0, 3, and 6), at telephone evaluations every 2 weeks, and via patient-completed side effect diaries. The study investigators and safety monitoring committee reviewed adverse events and made decisions regarding drug withdrawals, suspensions, and dose reductions as needed.

Time frame: 6 months

Population: Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment.