A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease Experiencing End of Dose "Wearing-Off" (TOZ-PD)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 449
- 主要终点
- Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time
研究概览
简要总结
Phase 3, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 3-arm safety and efficacy study (Part A) with an open-label phase (Part B).
详细描述
During Part A, each patient will participate for up to 30 weeks, which includes a Screening Period of 1 to ≤ 6 weeks, followed by a Baseline Visit and 24 weeks of double-blind treatment:
- Screening Period: 1 - 6 weeks.
- Double-Blind Treatment Period: 24 weeks.
After completion of Part A, patients will continue in Part B for an additional 56 weeks:
- Open-Label Treatment Period: 52 weeks.
- Post-Treatment Safety Follow Up: 4 weeks.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Patient understands study requirements and has given his/her written informed consent on an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved consent form.
- •Parkinson's disease diagnosis consistent with UK Parkinson's Disease Society Brain Bank Diagnostic criteria
- •Minimum of 3 years since diagnosis.
- •Meet Hoehn and Yahr PD stage
- •Good response to levodopa
- •Stable regimen of anti-PD medications
- •Patients must have been taking a levodopa-containing anti-PD medication continuously for at least the previous 12 months
- •Patient has documented a minimum amount of Off time.
- •If of childbearing potential (male and female) must use an acceptable method of contraception
排除标准
- •Previous tozadenant study participation
- •Current or recent participation in another study.
- •Secondary or atypical parkinsonism
- •Neurosurgical intervention for PD
- •Patient is taking apomorphine, budipine, istradefylline, tolcapone, or DUOPA™/Duodopa®
- •Treatment with excluded medications
- •Untreated or uncontrolled hyperthyroidism or hypothyroidism
- •Clinically significant out-of-range laboratory
- •MMSE out of range
- •Current episode of major depression (stable treatment for depression is permitted).
- •Recent suicide attempt or suicidal ideation type 4 or type 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS)
- •Women lactating or pregnant
- •Hypersensitivity to any components of tozadenant or excipients
- •Abnormal findings on the physical or neurological examination, or medical history that would make the patient unsuitable for the study
- •History of hepatitis or cholangitis
研究组 & 干预措施
Tozadenant 60 mg BID
During Part A, patients took two (2) tablets, one 60 mg tozadenant and one placebo, by mouth BID for a total of four (4) tablets per day.
Upon completion of Part A, all patients will begin dosing with open label tozadenant in Part B.
干预措施: tozadenant (Drug)
Tozadenant 120 mg BID
During Part A, patients took two (2) tablets of 60 mg tozadenant, by mouth BID for a total of four (4) tablets per day.
Upon completion of Part A, all patients will begin dosing with open label tozadenant in Part B.
干预措施: tozadenant (Drug)
Placebo BID
During Part A, patients took two (2) tablets of placebo, by mouth BID for a total of four (4) tablets per day.
Upon completion of Part A, all patients will begin dosing with open label tozadenant in Part B.
干预措施: placebo (Drug)
结局指标
主要结局
Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time
时间窗: Baseline to 24 Weeks
Awake time in OFF state (hr) is the average of maximum of 3 days diary. The primary efficacy endpoint was the change from baseline to Week 24 in OFF time, where OFF time in the Hauser Parkinson's Disease Home Diary (PD) was averaged over 3 days prior to the study visit. During Screening and through Part A of the study, the Hauser Parkinson's Disease Home Diary (PD) was completed on specified days directly preceding the scheduled study visits/assessments. Motor activity was recorded as OFF, ON (mobility improved), or asleep time. Patients were asked to record ON time according to dyskinesia categories "without dyskinesia", "with non troublesome dyskinesia" or "with troublesome dyskinesia". Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep.
次要结局
- Change in Good ON Time From Baseline to Week 24(Baseline to 24 Weeks)
- Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function(Baseline to Week 24)
- Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl(Baseline to Week 24)