An Open-Label, Randomized, Cross-Over Study to Investigate the Efficacy and Safety of Mexiletine PR Compared to Mexiletine IR

Not Applicable

Not yet recruiting

• Conditions: Myotonia
• Interventions: Drug: Granular powder in unit dose foil-lined sachet Mexiletine (PR); Drug: Oral Capsule Mexiletine (IR)

• Registration Number: NCT07097701
• Lead Sponsor: Lupin Ltd.

Brief Summary

An Open-Label, Randomized, Cross-Over Study to Investigate the Efficacy and Safety of Mexiletine PR compared to Mexiletine IR in Patients with Non-Dystrophic Myotonias (ACHILLES study)

Detailed Description

This is a multicenter, open-label, randomized, cross-over study intended to evaluate the efficacy and the safety of mexiletine PR (QD) vs mexiletine IR (TID) in patients with non-dystrophic myotonias including myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM). The study will consist of a 4-week screening period followed by two 12-week treatment periods. Eligible patients will be randomized to receive mexiletine PR or mexiletine IR for 12 weeks. After a wash out period of at least 7 days the patients will receive the opposite treatment for 12 weeks.

A total of 24 patients are planned to be enrolled (with a target enrollment of 12 naïve to previous mexiletine treatment and 12 previously treated with mexiletine).

Safety assessments include patient- and physician-reported adverse event reporting, electrocardiogram (ECG), standard clinical laboratory evaluations, physical examinations, and vital signs. Efficacy assessments include patient-reported outcomes (PROs) and functional capacity outcome measures.

Study Timeline

• Study First Submitted: 2024-11-21
• Status Verified: 2025-07
• Study First Submitted QC: 2025-07-24
• Study Start: 2025-07-30
• Last Update Submitted: 2025-07-30
• Study First Posted: 2025-07-31
• Last Update Posted: 2025-08-03
• Primary Completion: 2026-07-08
• Study Completion: 2026-10-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Mexiletine prolonged-release (PR)	Granular powder in unit dose foil-lined sachet Mexiletine (PR)	Mexiletine PR 167 mg (mexiletine HCl 200 mg) Mexiletine PR 333 mg (mexiletine HCl 400 mg) OR Mexiletine PR 500 mg (mexiletine HCl 600 mg)
Mexiletine immediate release (IR)	Oral Capsule Mexiletine (IR)	Mexiletine IR 167 mg (mexiletine HCl 200 mg)

Primary Outcome Measures

Name	Time	Method
To compare the safety of mexiletine PR vs mexiletine IR by incidence of treatment emergent Adverse Events (TEAEs), treatment-related TEAEs, serious AEs, and patient discontinuation rate between mexiletine PR and mexiletine IR after 12 weeks of treatment.	Baseline to week 24	To compare the safety of mexiletine PR vs mexiletine IR for the symptomatic treatment of myotonia in adult patients with non-dystrophic myotonias (myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM)) by incidence of treatment emergent Adverse Events (TEAEs), treatment-related TEAEs, serious AEs, and patient discontinuation rate between mexiletine PR and mexiletine IR after 12 weeks of treatment.
To compare the safety of mexiletine PR vs mexiletine IR by mean change from baseline in QTc intervals by12-lead in ECG	Baseline to week 24	To compare the safety of mexiletine PR vs mexiletine IR for the symptomatic treatment of myotonia in adult patients with non-dystrophic myotonias (myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM)) by mean change from baseline in QTc Intervals by12-lead in ECG
To compare the safety of mexiletine PR vs mexiletine IR by mean change from baseline in PR intervals by12-lead in ECG	Baseline to week 24	To compare the safety of mexiletine PR vs mexiletine IR for the symptomatic treatment of myotonia in adult patients with non-dystrophic myotonias (myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM)) by mean change from baseline in PR intervals by12-lead in ECG.
To compare the safety of mexiletine PR vs mexiletine IR by mean change from baseline in QRS intervals by12-lead in ECG	Baseline to week 24	To compare the safety of mexiletine PR vs mexiletine IR for the symptomatic treatment of myotonia in adult patients with non-dystrophic myotonias (myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM)) by mean change from baseline in QRS intervals by12-lead in ECG
To compare the safety of mexiletine PR vs mexiletine IR by mean change from baseline by average minimum heart rate by12-lead in ECG	Baseline to week 24	To compare the safety of mexiletine PR vs mexiletine IR for the symptomatic treatment of myotonia in adult patients with non-dystrophic myotonias (myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM)) by mean change from baseline in average heart rate by 12-lead in ECG
To compare the safety of mexiletine PR vs mexiletine IR by performing physical examiniations	Baseline to week 24	To compare the safety of mexiletine PR vs mexiletine IR for the symptomatic treatment of myotonia in adult patients with non-dystrophic myotonias (myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM)) by performing physical examinations. The investigator will complete a physical examination including the following regions and systems: general appearance, head and neck, heart, lung, abdomen, chest and back, upper extremities, lower extremities, neurological, and dermatological. In addition, height and weight will be recorded.
To compare the safety of mexiletine PR vs mexiletine IR by assessing vital signs	Baseline to week 24	To compare the safety of mexiletine PR vs mexiletine IR for the symptomatic treatment of myotonia in adult patients with non-dystrophic myotonias (myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM)) by assessing vital signs. Vital signs will be obtained at each study visit and will include pulse, respiration, body temperature, and blood pressure. Unscheduled vital sign measurements may be obtained at the investigator's discretion during the study.
To compare the safety of mexiletine PR vs mexiletine IR by performing standard clinical laboratory evaluations	Baseline to week 24	To compare the safety of mexiletine PR vs mexiletine IR for the symptomatic treatment of myotonia in adult patients with non-dystrophic myotonias (myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM)) by performing standard clinical laboratory evaluations. Clinical laboratory samples will be collected under fasting conditions and hematology, serum chemistry, and urinalysis assessments will be performed

Secondary Outcome Measures

Name	Time	Method
Mean change in handgrip relaxation time	Baseline to week 24	Opening Time (VHOT) functional evaluation by mean change in maximal voluntary isometric contraction (MVIC) and relaxation time by Video-recording of Hand. The dominant wrist and hand are placed on a bedside table with the forearm fully supinated. The patient is asked to open the hand after making a tight fist for 3-5 seconds 2 times within 30 minutes.
Mean change in health-related quality of life	Baseline to week 24	Mean change in health-related quality of life (measured by INQoL) on a 7-point Likert scale
Mean change in MBS scores	Baseline to week 24	Mean change in Myotonia Behavior Scale (MBS) scores on a 0-5 rating scale
Mean change in time to perform Timed-up and go (TUG) test	Baseline to week 24	Mean change in time (seconds) to perform Timed-up and go (TUG) test
Mean change in VAS	Baseline to week 24	Score for muscle stiffness (myotonia severity) as self-reported by patients on a Visual Analog Scale (VAS) on a 1-100 rating scale.
Mean change in Clinical Global Impression (CGI) - Efficacy Scale	Baseline to week 24	Score for Clinical Global Impression (CGI) - Efficacy by a 5 rating scale of No Symptoms to Very Severe
Mean change in Clinical Global Impression (CGI) - Tolerability Index Scale	Baseline to week 24	Mean change in Clinical Global Impression (CGI) - Tolerability Index Scale by a 7 rating scale of much worse to much better
Mean change in time to perform the 10-meter Walk Test	Baseline to week 24	Mean change in time (seconds) to perform the 10-meter Walk Test (10mWT) 10mWT is a performance-based test assessing walking in two different conditions, own preferred speed and maximum speed, over a short distance. The time taken to walk 10 meters at usual comfortable and maximum speed is recorded with a stopwatch.
Mean change in Gastrointestinal function: The Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQoL)	Baseline to week 24	Mean change in Gastrointestinal function: The Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQoL) by a 5 scale of no symptoms to Symptoms are incapacitating, unable to do daily activities
Mean change in CMRS Scale	Baseline to week 24	Mean change in Clinical myotonia rating scale (CMRS)
Mean change Swallowing function	Baseline to week 24	Mean change in Swallowing function: timed testing of swallowing
Preference between the two study treatments	Baseline to week 24	Patients were also asked to give their preference between the 2 periods of treatment and to provide the primary reasons for their choice.