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)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Lupin Ltd.
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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)
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Study drug (mexiletine PR or mexiletine IR) will be started as a 167 mg once a day (QD) treatment regimen. The dose will be titrated up at Week 1 to 333 mg and at Week 2 to a maximum dose of 500 mg. All dose escalations will be done with safety ECG assessments using portable ECG device. Study drug should be taken at the beginning of the meal at approximately the same time of the day every day, preferably in the morning for Mexiletine PR or Mexiletine IR QD. Mexiletine IR twice a day (BID) should be taken in the morning and afternoon and Mexiletine IR TID should be taken in the morning, afternoon, and evening.
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Mexiletine prolonged-release (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)
干预措施: Granular powder in unit dose foil-lined sachet Mexiletine (PR) (Drug)
Mexiletine immediate release (IR)
Mexiletine IR 167 mg (mexiletine HCl 200 mg)
干预措施: Oral Capsule Mexiletine (IR) (Drug)
结局指标
主要结局
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.
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- Mean change in handgrip relaxation time(Baseline to week 24)
- Mean change in health-related quality of life(Baseline to week 24)
- Mean change in MBS scores(Baseline to week 24)
- Mean change in time to perform Timed-up and go (TUG) test(Baseline to week 24)
- Mean change in VAS(Baseline to week 24)
- Mean change in Clinical Global Impression (CGI) - Efficacy Scale(Baseline to week 24)
- Mean change Swallowing function(Baseline to week 24)
- Mean change in Clinical Global Impression (CGI) - Tolerability Index Scale(Baseline to week 24)
- Mean change in time to perform the 10-meter Walk Test(Baseline to week 24)
- Mean change in Gastrointestinal function: The Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQoL)(Baseline to week 24)
- Mean change in CMRS Scale(Baseline to week 24)
- Preference between the two study treatments(Baseline to week 24)