Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 5
- 主要终点
- Clinical Global Impression Scale
研究概览
简要总结
Parkinson's disease (PD) is a progressive neurodegenerative disease. Symptomatic therapy is primarily aimed at restoring dopamine function in the brain. Oral selegiline in conjunction with L-dopa has been a mainstay of therapy for PD patients experiencing motor fluctuations for many years. The mechanisms accounting for selegiline's beneficial adjunctive action in the treatment of PD are not fully understood. Inhibition of monoamine oxidase (MAO) type B (MAO-B) activity is generally considered to be of primary importance.
Oral selegiline has low bio-availability and is typically dosed BID, for a total of 5-10 mg daily. Recently, the FDA approved a new orally disintegration tablet (ODT) formulation of selegiline, called ZelaparTM. This new formulation utilizes Zydis technology to dissolve in the mouth, with absorption through the oral mucosa, thereby largely bypassing the gut and avoiding first pass hepatic metabolism. This allows more active drug to be delivered at a lower dose. Consequently, Zelapar is dosed once-daily, up to 2.5 mg per day. There are no empirical data indicating whether the use of the new approved formulation of selegiline ODT (Zelapar) is superior or preferred by patients compared to traditional oral selegiline. It is believed that clinical efficacy will be preserved or enhanced, by delivering more active drug, with improved patient preference for the ODT formulation due to the once-daily dosing .
The effectiveness of orally disintegrating selegiline as an adjunct to carbidopa/levodopa in the treatment of PD was established in a multicenter randomized placebo-controlled trial (n=140; 94 received orally disintegrating selegiline, 46 received placebo) of three months' duration. Patients randomized to orally disintegrating selegiline received a daily dose of 1.25 mg for the first 6 weeks and a daily dose of 2.5 mg for the last 6 weeks. Patients were all treated with levodopa and could additionally have been on dopamine agonists, anticholinergics, amantadine, or any combination of these during the trial. At 12 weeks, orally disintegrating selegiline-treated patients had an average of 2.2 hours per day less "OFF" time compared to baseline. Placebo treated patients had 0.6 hours per day less "OFF" time compared to baseline. These differences were significant (p < 0.001). Adverse events were very similar between drug and placebo.
详细描述
This is an open label, multicenter, 6 week study of the conversion from oral selegiline to orally disintegrating selegiline in PD patients with or without motor fluctuations, and currently taking levodopa. The study consists of the substitution of the oral selegiline with 1.25 mg of orally disintegrating selegiline for 10 days, and up titration of orally disintegrating selegiline to 2.5 mg per day for the next 30 days. The study will consist of 2 study visits in the clinic: Baseline and Day 40, and a telephone visit at Day 10.
Inclusion Criteria:
- Idiopathic PD confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity 2. Male or female outpatients 3. Age 30-90 years 4. Current use of levodopa and oral selegiline (5-10 mg /day), stable for at least 1 month and well tolerated 5. Positive treatment response to current anti-parkinsonian medications in the opinion of the investigator 6. Acceptable contraception for females of child bearing potential 7. Willing and able to comply with study procedures. 8. Willing and able to give written informed consent prior to beginning any study procedures.
Exclusion Criteria:
- Atypical parkinsonism due to drugs, metabolic disorders, encephalitis, trauma, or other neurodegenerative diseases. 2. Significant cognitive or psychiatric impairment which, in the opinion of the investigator, would interfere with the ability to complete all the tests required in the protocol. 3. Participation in another clinical drug trial within the previous four weeks. 4. Patients on any medications contraindicated with Zelapar (including meperidine/Demerol, tramadol, methadone, propoxyphene, dextromethorphan, other selegiline products) 5. Patients with a known hypersensitivity to any formulation of selegiline or any of the inactive ingredients of Zelapar, or previous exposure to orally disintegrating selegiline 6. History of melanoma 7. Unstable/uncontrolled medical problems 8. History of drug/alcohol abuse 9. Patients currently taking rasagiline
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic PD confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity
- •Male or female outpatients
- •Age 30-90 years
- •Current use of levodopa and oral selegiline (5-10 mg /day), stable for at least 1 month and well tolerated
- •Positive treatment response to current anti-parkinsonian medications in the opinion of the investigator
- •Acceptable contraception for females of child bearing potential
- •Willing and able to comply with study procedures.
- •Willing and able to give written informed consent prior to beginning any study procedures.
排除标准
- •Atypical parkinsonism due to drugs, metabolic disorders, encephalitis, trauma, or other neurodegenerative diseases.
- •Significant cognitive or psychiatric impairment which, in the opinion of the investigator, would interfere with the ability to complete all the tests required in the protocol.
- •Participation in another clinical drug trial within the previous four weeks.
- •Patients on any medications contraindicated with Zelapar (including meperidine/Demerol, tramadol, methadone, propoxyphene, dextromethorphan, other selegiline products)
- •Patients with a known hypersensitivity to any formulation of selegiline or any of the inactive ingredients of Zelapar, or previous exposure to orally disintegrating selegiline
- •History of melanoma
- •Unstable/uncontrolled medical problems
- •History of drug/alcohol abuse
- •Patients currently taking rasagiline
研究组 & 干预措施
Selegiline
Open label switch from current oral selegiline dose to orally disintegrating selegiline (Zelapar) titrated to a dose of 2.5 mg QD.
干预措施: Zelapar (Drug)
结局指标
主要结局
Clinical Global Impression Scale
时间窗: baseline versus 40 days
Baseline assessments included a clinical global impression scale. This is compared to day 40 assessment. The clinical global impression scale consists of a 3-item observer-rated scale that measures illness severity, global improvement or change and therapeutic response. Each item is rated between 1-7. The minimum score is 3. The maximum score is 21. A score of 3 means the patient's symptoms are very much improved. A score of 21 means the patient is very much worse.
次要结局
- MDS-UPDRS Scale at Baseline and Day 40(baseline versus day 40)
研究者
Joseph Jankovic
Professor
Baylor College of Medicine