A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Investigate the Efficacy and Safety of Once Daily Mexiletine PR During 26 Weeks of Treatment in Patients With Myotonic Dystrophy Type 1 and Type 2 (Phase 3)
概览
- 阶段
- 3 期
- 干预措施
- Placebo
- 疾病 / 适应症
- Myotonic Dystrophy
- 发起方
- Lupin Ltd.
- 入组人数
- 176
- 试验地点
- 7
- 主要终点
- To assess the efficacy of once daily mexiletine PR for the symptomatic treatment of myotonia in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2).
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
A Randomized, Double-blind, Placebo-Controlled, Multi-Center Study to Investigate the Efficacy and Safety of Once Daily Mexiletine PR During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 (HERCULES study)
详细描述
This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled study intended to evaluate the efficacy and the safety of mexiletine PR in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2). The study will consist of a 4- week screening period and a 26-week treatment phase with patient visits at screening, baseline, Weeks 1, 2, 14, and 26. Eligible patients will be randomized to mexiletine or placebo in a 1:1 ratio. Approximately 80 DM1 patients (40 active: 40 placebo) are planned to be enrolled. For the purpose of sample size re-estimation, an interim analysis will be conducted when a total of 40 patients in total complete/early terminate the study. In addition, 16 DM2 patients are planned to be enrolled (sub-group - 8 active: 8 placebo).
研究者
入排标准
入选标准
- •DM1 or DM2 diagnosis confirmed genetically;
- •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);
- •Ability to understand the study requirements including intention to stay in the study until the end-of-study visit at 26 weeks of treatment;
- •Male or non-pregnant female ≥16 years of age;
- •Body Mass Index (BMI) of 18.5 kg/m2 to 30 kg/m2, and weight ≥45 kg;
- •Female patients of childbearing potential must be using a highly effective form of birth control for the duration of the study and for at least 7 days after last dose of study drug;
- •No significant cardiac abnormalities as determined by a cardiologist's assessment;
- •Have sufficient finger flexor strength to grasp the handle of the dynamometer used to measure myotonia;
- •Presence of clinical handgrip myotonia (delayed relaxation of grip of ≥ 3 seconds after maximum voluntary contraction) at screening using VHOT;
- •Be able to walk independently 10 meters (cane, walker, orthoses allowed);
排除标准
- •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;
- •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;
- •Medical conditions that could affect hand functioning including but not limited to rheumatoid arthritis, Dupuytren's contracture, hand deformity, etc.;
- •Severe arthritis or medical condition (other thanDM1/DM2) that would significantly impact ambulation;
- •High incidence of falls or fall-associated fractures (\>5 falls during the past 12 months);
- •Preexisting elevated liver function tests \> 3 times the upper limit of normal (ULN) at screening (alanine transaminase (ALT)/aspartate transaminase (AST), gamma-glutamyl transferase (GGT)) and/or any abnormal chemistry, hematology or urine lab considered clinically significant by investigator;
- •Serum potassium values \< 3.5 mmol/L or \> 5.0 mmol/L or serum magnesium values \< 1.7 mg/dL. Electrolytic imbalance such as hypokalaemia, hyperkalaemia or hypomagnesaemia may increase the proarrhythmic effects of mexiletine. Electrolyte imbalances need to be corrected before administering mexiletine and will be monitored throughout treatment.
- •Treatment with mexiletine within 4 weeks prior to baseline (Day 1);
研究组 & 干预措施
Placebo
0 mg (matching sachet volumes to low, medium and high dose active drug)
干预措施: Placebo
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: Mexiletine granules for prolonged-release oral suspension
结局指标
主要结局
To assess the efficacy of once daily mexiletine PR for the symptomatic treatment of myotonia in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2).
时间窗: 26 weeks
Handgrip relaxation time in DM1 patients by mean change in baseline of handgrip relaxation time (seconds) after maximal voluntary isometric contraction (MVIC)
次要结局
- Mean change in DM1-Activ-c scale (DM1 patients only)(26 weeks)
- Mean change in time to perform the 10-meter Walk Test(26 weeks)
- Mean change in handgrip relaxation time(26 weeks)
- Mean change in time to perform Timed-up and go (TUG) test(26 Weeks)
- Mean change in health-related quality of life measured by EQ-5D(26 weeks)
- Mean change in Myotonic Dystrophy Health Index (MDHI) score (DM1 patients)(26 weeks)
- Assess the safety of mexiletine PR by vital signs(26 weeks)
- Assess the safety of mexiletine PR by physical examinations(26 weeks)
- Mean change in health-related quality of life(26 weeks)
- Mean change in Myotonic Dystrophy 2 Health Index (MD2HI) score (DM2 patients)(26 weeks)
- Assess the safety of mexiletine PR by changes in ECG(26 weeks)
- Mean change in MBS scores(26 weeks)
- Mean change in VAS(26 weeks)
- Assess the safety of mexiletine PR by standard clinical laboratory evaluations(26 weeks)
- Assess the safety of mexiletine PR by AEs(26 weeks)
- To assess the pharmacokinetics of mexiletine PR(26 weeks)
- To assess the pharmacokinetics of mexiletine PR by AUC0-t(26 weeks)
- To assess the pharmacokinetics of mexiletine PR by Cmax(26 weeks)
- To assess the safety of once daily mexiletine PR for the symptomatic treatment of myotonia in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2).(26 weeks)