A Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Safinamide 100mg Once Daily, as add-on Therapy, in Idiopathic Parkinson's Disease (PD) Patients With Motor Fluctuations and PD Related Chronic Pain
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Zambon SpA
- 入组人数
- 94
- 试验地点
- 45
- 主要终点
- Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set
研究概览
简要总结
Primary objective:
• To evaluate the potential efficacy of safinamide 100 mg once daily (OD), compared with placebo, as add-on therapy for PD-related chronic pain
Secondary objectives:
- Percentage of pain responders
- Clinical Global Impression for pain
- Patient Global Impression for pain
- Reduction in use of pain drugs
- Mood
- Motor and non-motor symptoms
Safety Objectives:
• Safety and tolerability
详细描述
This is a Phase IV, international, multicentre, randomised, double-blind, placebo controlled study in idiopathic Parkinson's disease (IPD) patients, experiencing motor fluctuations and PD-related chronic pain while on stable doses of levodopa (L-Dopa), to Evaluate the Efficacy and Safety of Safinamide 100 mg Once Daily, as Add-On Therapy.
The study consisted of:
- A screening period of up to 1 to 2 weeks.
- A treatment period of 16 weeks.
- A telephone follow-up call at 1 week after the end of treatment. Eligible subjects were randomly assigned in a ratio of 2:1 to receive either safinamide (50 mg or 100 mg) or matching placebo. At Day 1, eligible subjects entered the treatment period to receive safinamide 50 mg (from Day 1 to Day 7) and then 100 mg (from Day 8 onwards) orally OD. After completion of all baseline assessments, subjects received the first dose of study drug at the study center and, thereafter, study drug was to be taken at home each morning along with their first morning dose of L-DOPA and other (if any) PD medications. On Day 8, the dose of study drug was increased, at home, to 100 mg OD. Each subject received treatment for 16 weeks, with visits at Week 0/Day 1 (baseline) and at Weeks 4, 8, and 16 (or early termination). From Day 1 onwards, subjects recorded the use of as-needed (PRN) medications along with indicating the worst pain they experienced on a daily basis.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 30 years of age or older, at the time of signing the informed consent.
- •Diagnosed with IPD by using the United Kingdom Parkinson's Disease Society Brain Bank criteria for more than 5 years duration.
- •Receiving treatment with a stable dose of oral L-Dopa (including controlled release [CR], immediate release [IR] or a combination of CR/IR), with and without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor and may be receiving concomitant treatment with stable doses of a dopamine agonist, an anticholinergic and/or amantadine for at least 4 weeks prior to the randomisation (baseline visit).
- •Hoehn and Yahr stage between 2-3 (inclusive) during the "ON" phase at the screening visit.
- •Experiencing motor fluctuations following optimum titration of treatment medications and within the 4 weeks immediately prior to randomisation.
- •Experiencing chronic pain (i.e. ongoing for ≥3 months prior to screening visit); the Investigator must consider chronic pain directly related to PD and not explained by any other health problem (e.g. peripheral neuropathy, organ disease or arthritis pain) OR consider the intensity of chronic pain specifically aggravated by PD.
- •If taking regular analgesics, the treatment regimen should be stable in the 4 weeks prior to the randomisation visit.
- •Able to maintain an accurate and complete electronic diary with the help of a caregiver.
- •Male or female
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i.Not a woman of childbearing potential (WOCBP) OR ii.A WOCBP who agrees to follow the contraceptive guidance
- •Capable of giving signed informed consent
排除标准
- •Any form of Parkinsonism other than IPD.
- •Diagnosis of chronic migraine (>15 days per month) or cancer pain.
- •History of bipolar disorder, depression, schizophrenia or other psychotic disorder requiring treatment with neuroleptics.
- •History of dementia or cognitive dysfunction.
- •Severe, peak dose or biphasic dyskinesia.
- •Unpredictable or widely swinging fluctuations.
- •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.
- •Moderate or severe liver failure using the Child-Pugh classification score.
- •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.
- •Allergy/sensitivity, intolerance or contraindications to Safinamide.
- •Treatment with monoamine oxidase inhibitors (MAOIs), levodopa infusion, pethidine, fluoxetine, fluvoxamine less than 4 weeks prior to the randomisation visit
- •Use of any investigational drug or device within 30 days prior to screening or 5 half-lives, whichever is the longest
- •Previous treatment with Safinamide in the 9 months before the screening visit
- •Mini-Mental State Exam (MMSE) total score <24 at screening.
- •NRS score ≤ 4 points at randomization visit.
- •Any clinically significant condition which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for participants while in the study
研究组 & 干预措施
Experimental
Safinamide methanesulfonate film coated tablets once daily, 50 mg and 100 mg. Safinamide methanesulfonate 50 mg and 100 mg tablets was administered orally, OD, with or without food, at breakfast time when the subject was taking their morning dose of L-DOPA.
Subjects received study drug 50 mg (from Day 1 to Day 7) and then 100 mg (from Day 8 onwards). The dose of 100 mg/day (titrated from 50 mg/day after 1 week) was selected based on the results of previous studies in patients with PD and from the results of a post hoc analysis that investigated the effects of safinamide on pain.
干预措施: Safinamide Methanesulfonate (Drug)
Placebo
Safinamide methanesulfonate matching placebo film coated tablets once daily. The matching placebo was administered orally, OD, in tablets, with or without food, at breakfast time when the subject was taking their morning dose of L-DOPA.
干预措施: Safinamide methanesulfonate matching placebo (Other)
结局指标
主要结局
Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Full Analysis Set
时间窗: Baseline and Week 16
To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity ("average worst pain experienced in the last 7 days"), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.
Change From Baseline to Week 16 in Pain Severity (NRS-11 Scale) - Per Protocol Set
时间窗: Baseline and Week 16
To evaluate the potential efficacy of safinamide 100 (mg od), compared to placebo, as add-on therapy, for change pain severity ("average worst pain experienced in the last 7 days"), as assessed by an 11-point Numerical Rating Scale (NRS). Based on this scale, 0 point is the minimum and 10 point is the maximum. The higher the score, the more severe the pain.
次要结局
- Number of Subjects With a Reduction of ≥2 Points in Pain Severity at Week 16, Compared to Baseline(Week 16)
- The Change From Baseline to Week 16 in the Clinical Global Impression of Change (CGI-C) Score for Pain(Baseline and Week 16)
- The Global Impression of Severity (CGI-S) Score for Pain at Week 16(Baseline and Week 16)
- Number of Subjects With Concomitant Use of Pain Drugs at Different Timepoints(Baseline, weeks 4, 8 and 16)
- Amount of PRN PD Pain Medication: Count of Subjects Who Used PRN PD Pain Medication in the 7 Days Preceding Visits(at Baseline and weeks 4, 8 and 16)
- Amount of PRN PD Pain Medication: Number of Days on Which PRN PD Pain Medication Was Taken at Different Timepoints(At Baseline and weeks 4, 8 and 16)
- The Change From Baseline to Week 16 in MDS-UPDRS(Baseline and Week 16)
- The Change From Baseline to Week 16 in the Patient Global Impression of Change (PGI-C) Score for Pain(Baseline and Week 16)
- Change From Baseline to Week 16 in the Hospital Anxiety and Depression Scale (HADS) Score(Baseline and Week 16)