12-weeks, Multicentre, Randomized, Double-blind, Placebo-controlled, Exploratory, Pilot Study to Evaluate the Safety and Efficacy of Safinamide 200 mg OD, as add-on Therapy, in Patients With Possible or Probable Parkinsonian Variant of MSA
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Zambon SpA
- 入组人数
- 49
- 试验地点
- 19
- 主要终点
- TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)
研究概览
简要总结
The study is a placebo controlled study, with two parallel arms, in which participants will be randomly assigned in a 2:1 ratio to receive either active (200 mg safinamide) or placebo in a double blind manner. Study population is patients diagnosed, with possible or probable parkinsonian variant of Multiple System Atrophy who are on a stable treatment of levodopa
详细描述
The overall design is a parallel group, placebo controlled, double blind study. The target population are participants diagnosed with possible or probable parkinsonian variant of Multiple System Atrophy who are on stable doses of levodopa.
Trial participation will be up to a maximum duration of 14 weeks and will comprise a screening period (up to 2 weeks), a 2-week run in period during which subjects will receive 1 tablet (either 100 mg safinamide or matching placebo), followed by a 10-week period, during which study participants will take 2 tablets of study medication (200 mg safinamide or placebo) once daily, taken in the morning in addition to their morning levodopa dose. A telephone follow-up call will be performed 2 weeks after the end of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 30 to 80 years of age inclusive, at the time of signing the informed consent;
- •Participants who are diagnosed (with MRI confirmation) with possible or probable parkinsonian variant of Multiple System Atrophy less than 2 years ago;
- •Participants with an anticipated survival of at least 3 years in the opinion of the investigator;
- •Female not pregnant, not breastfeeding, and at least one of the following conditions applies:
- •Not a woman of childbearing potential OR
- •A woman of childbearing potential who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study intervention;
- •Capable of giving signed informed consent
排除标准
- •History of neurosurgical procedure, including stereotactic surgery;
- •History of Deep Brain Stimulation (DBS);
- •History of bipolar disorder, severe depression, schizophrenia or other psychotic disorder;
- •History of drug and/or alcohol abuse within 12 months prior to screening as defined by the current edition of the Diagnostic and Statistical Manual of Mental Disorders;
- •History of dementia (DSM-V criteria);
- •Ophthalmologic history including any of the following conditions: albinism, uveitis, retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive diabetic retinopathy, inherited retinopathy or family history of hereditary retinal disease;
- •Active hepatitis B or C;
- •History of human immunodeficiency virus (HIV) infection;
- •Subjects not able to swallow oral medications;
- •Subjects with severe orthostatic symptoms;
- •Impaired ambulation, i.e. falling more than once per week, bedridden patients or confined to a wheelchair during the whole day;
- •Subjects with active malignant neoplasms;
- •Movement disorders other than MSA (e.g. Parkinson Disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, pharmacological or post-encephalic parkinsonism);
- •Any clinically significant or unstable medical or surgical condition that, in the opinion of the investigator, might preclude safe completion of the study or might affect the results of the study;
- •Not on a stable regime, for at least 4 weeks prior to the randomization (baseline visit), of
- •oral levodopa (including controlled release, immediate release or a combination of controlled release/immediate release), with or without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor or
- •dopamine agonist, anticholinergic and/or amantadine.
- •Patients should not have received treatment with monoamine oxidase inhibitors in the 2 weeks prior to the randomization visit, nor treatment with levodopa infusion, pethidine, opiates, opioids, fluoxetine, fluvoxamine in the 4 weeks prior to the randomization visit;
- •Patients should not have received treatment with an oral or depot neuroleptic within 12 weeks prior to the randomization visit;
- •Use of any investigational drug within 30 days prior to screening or 5 half-lives, whichever is the longest;
- •Montreal Cognitive Assessment (MoCA) ≤ 20;
- •Laboratory assessments showing moderate or severe hepatic impairment (2x ULN);
- •Allergy/sensitivity or contraindications to the investigational medicinal products (IMPs) or their excipients, anticonvulsants, levodopa or other anti-parkinsonian drugs;
- •Any clinically significant condition which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for patients while in the study.
研究组 & 干预措施
Active
Safinamide methanesulfonate film-coated tablets once daily
干预措施: Safinamide Methanesulfonate (Drug)
Placebo
Safinamide Methanesulfonate matching placebo film-coated tablets once daily
干预措施: Safinamide Methanesulfonate matching placebo (Drug)
结局指标
主要结局
TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)
时间窗: Throughout the study, from baseline (and at each interim visit) to telephone follow-up visit at 14 week.
While evaluating safety and tolerability of safinamide, 200 mg od, compared with placebo, severity of TEAEs, their relationship to study drug, their seriousness and their consequences were assessed. TEAEs were defined as adverse events (AEs) that started after the first dose of study drug.
次要结局
- Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (PP Population)(From baseline to week 12)
- Change From Baseline to Week 12 in Montreal Cognitive Assessment (MoCA) Scale(From baseline to week 12)
- Change From Baseline to Week 12 in the Goniometric Measurement for Anterior Displacement(From baseline to week 12)
- Change From Baseline to Week 12 in the Goniometric Measurement for Lateral Displacement(From baseline to week 12)
- Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (ITT Population)(From baseline to week 12)
- Change From Baseline to Week 12 in Multiple System Atrophy Health-Related Quality of Life (MSA-QoL) Scale(From baseline to week 12)
- Change From Baseline to Week 12 in Unified Dystonia Rating Scale (UDRS)(From baseline to week 12)