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)
Ability to comprehend and willingness to sign an informed consent (ICF) or ICF of the parent(s)/legal guardian and written assent from the patient (if patient < 18 years of age);
Non-dystrophic myotonias including myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM) confirmed genetically;
Male or non-pregnant female ≥16 years and older at screening;
Body Mass Index (BMI) of 18.5 kg/m2 to 30 kg/m2, and weight ≥45 kg;
Are pregnant or lactating;
Have any one of the following medical conditions: uncontrolled diabetes mellitus, cancer other than skin cancer less than five years previously (e.g., basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) of skin allowed), multiple sclerosis, seizure disorders, or other serious medical illness or has any other condition, which in the opinion of the Investigator, precludes the participant's participation in the study or the participant is unlikely to comply with the protocol-defined procedures and therefore is unlikely to complete the study;
Severe renal impairment (glomerular filtration rate (GFR) < 30 mL/min);
Medical conditions which could interfere with muscle function such as infections, trauma, fractures, or planned surgery;
Crossover
Granular powder in unit dose foil-lined sachet Mexiletine (PR)
DrugMexiletine (PR)
Oral Capsule Mexiletine (IR)
DrugMexiletine (IR)
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.
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
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
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
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
Mean change in handgrip relaxation time
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
Mean change in health-related quality of life (measured by INQoL) on a 7-point Likert scale
Mean change in MBS scores
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
Mean change in time (seconds) to perform Timed-up and go (TUG) test
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Lupin Ltd.
Lead sponsor
Lupin Atlantis Holdings S.A.
Collaborator
