A Phase 2, 12-Week, Double-Blind, Dose-Finding, Placebo-Controlled Study to Assess the Efficacy and Safety of a Range of SCH 420814 Doses in Subjects With Moderate to Severe Parkinson's Disease Experiencing Motor Fluctuations and Dyskinesias
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 253
- 主要终点
- Change From Baseline to Endpoint of 12 Weeks in the 3-day Average of Awake Time Per Day Spent in the "Off" State
研究概览
简要总结
The purpose of the study is to assess the efficacy and safety of a range of doses of SCH 420814 (preladenant) when used together with a stable dose of L-dopa/dopa decarboxylase inhibitor to treat Parkinson's disease. In this study, we will be comparing 3 doses (1 mg, 2 mg, and 5 mg taken twice a day) of preladenant with placebo (sugar pill). Following an Interim Analysis (temporary hold for new enrollment-ongoing subjects will continue on treatment) to review drug safety, a new dose group of 10 mg (taken twice a day) may be added.
Approximately 160 participants will be randomized in this study in approximately 22 study centers worldwide for the first part of this study. Following the Interim Analysis, 40 new participants may be added, for a total of 200 participants. The study is double blind, which means neither you nor your study doctor will know whether you are receiving the study medication or placebo.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be 30 years of age, of either sex and of any race, with a diagnosis of moderate to severe idiopathic Parkinson's disease for at least 5 years.
- •Women of childbearing potential must have a negative serum pregnancy test at Visit 2 (Week -1). If participant is postmenopausal (not surgically induced), she must be postmenopausal by history for at least 2 years before study entry. If not, proper birth control must be used.
- •Note: Acceptable methods of birth control include oral or injectable hormonal contraceptive, medically prescribed intrauterine device (IUD), and double-barrier method (eg, condom in combination with spermicide). Bilateral tubal ligation is an acceptable method of birth control for this study.
- •Participants' clinical laboratory tests (complete blood count [CBC], blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator/sponsor.
排除标准
- •Participants with any form of drug-induced or atypical parkinsonism, cognitive impairment (Mini-Mental State Examination [MMSE] score <=23), a history of Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) diagnosed major depression, unstable mild depression or psychosis, or participants taking tolcapone will be excluded. (Participants with mild depression who are well controlled on a stable dose of an antidepressant medication for at least 4 weeks before screening will be eligible.)
- •All participants with a severe or ongoing unstable medical condition will be excluded including those with a history of poorly controlled diabetes, obesity associated with metabolic syndrome, uncontrolled hypertension, cerebrovascular disease, or any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, renal failure, history of abnormal renal function, seizures, alcohol/drug dependence, or previous surgery for Parkinson's disease.
- •Average daily consumption of more than two 4-oz (120 mL) glasses of wine or their equivalent.
- •Because it is not known whether preladenant passes into breast milk and because the effects, if any, of preladenant on the developing human are unknown, women who are breastfeeding or who are considering breastfeeding are excluded from this trial.
- •Participants with allergy/sensitivity to study drug or its excipients.
- •Participants with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.
- •Participants who have used any other investigational drugs within 30 days of Screening.
- •Participants who are participating in any other clinical study.
研究组 & 干预措施
Placebo BID
Participants received preladenant matching placebo BID during the 12-week treatment period.
干预措施: Placebo (Drug)
Preladenant 2 mg BID
Participants received preladenant 2 mg BID during the 12-week treatment period.
干预措施: Preladenant (Drug)
Preladenant 1 mg BID
Participants received preladenant 1 mg twice daily (BID) during the 12-week treatment period.
干预措施: Preladenant (Drug)
Preladenant 1 mg BID
Participants received preladenant 1 mg twice daily (BID) during the 12-week treatment period.
干预措施: L-dopa (Drug)
Preladenant 1 mg BID
Participants received preladenant 1 mg twice daily (BID) during the 12-week treatment period.
干预措施: Other Parkinson's Disease treatments (Drug)
Preladenant 2 mg BID
Participants received preladenant 2 mg BID during the 12-week treatment period.
干预措施: L-dopa (Drug)
Preladenant 2 mg BID
Participants received preladenant 2 mg BID during the 12-week treatment period.
干预措施: Other Parkinson's Disease treatments (Drug)
Preladenant 5 mg BID
Participants received preladenant 5 mg BID during the 12-week treatment period.
干预措施: Preladenant (Drug)
Preladenant 5 mg BID
Participants received preladenant 5 mg BID during the 12-week treatment period.
干预措施: L-dopa (Drug)
Preladenant 5 mg BID
Participants received preladenant 5 mg BID during the 12-week treatment period.
干预措施: Other Parkinson's Disease treatments (Drug)
Preladenant 10 mg BID
Participants received preladenant 10 mg BID during the 12-week treatment period.
干预措施: Preladenant (Drug)
Preladenant 10 mg BID
Participants received preladenant 10 mg BID during the 12-week treatment period.
干预措施: L-dopa (Drug)
Preladenant 10 mg BID
Participants received preladenant 10 mg BID during the 12-week treatment period.
干预措施: Other Parkinson's Disease treatments (Drug)
Placebo BID
Participants received preladenant matching placebo BID during the 12-week treatment period.
干预措施: L-dopa (Drug)
Placebo BID
Participants received preladenant matching placebo BID during the 12-week treatment period.
干预措施: Other Parkinson's Disease treatments (Drug)
结局指标
主要结局
Change From Baseline to Endpoint of 12 Weeks in the 3-day Average of Awake Time Per Day Spent in the "Off" State
时间窗: Baseline (Week -1) and up to 12 weeks
"Off" time refers to periods of inadequate control of Parkinson disease symptoms (worsening or presence of symptoms). For baseline and the 12 weeks treatment period, hours spent in the "off" state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. Change from baseline in least squares (LS) means and pooled standard deviation (SD) were obtained from an analysis of covariance (ANCOVA) model with effect for treatment and baseline covariate. A negative change from baseline signifies less time spent in the "off" state.
次要结局
- Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit(Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Awake Time Per Day Spent in the "on" State(Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias)(Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias)(Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias)(Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Absolute Duration of Dyskinesias(Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Total Sleep Time(Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Frequency of Sleep Attacks at Week 2(Baseline (predose Day 1) and 2 hours postdose at Week 2)
- Change From Baseline in Frequency of Sleep Attacks at Week 4(Baseline (predose Day 1) and 2 hours postdose at Week 4)
- Change From Baseline in Frequency of Sleep Attacks at Week 6(Baseline (predose Day 1) and 2 hours postdose at Week 6)
- Change From Baseline in Frequency of Sleep Attacks at Week 10(Baseline (predose Day 1) and 2 hours postdose at Week 10)
- Change From Baseline in UPDRS Part 2(Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Frequency of Sleep Attacks at Week 8(Baseline (predose Day 1) and 2 hours postdose at Week 8)
- Change From Baseline in Frequency of Sleep Attacks at Week 12(Baseline (predose Day 1) and 2 hours postdose at Week 12)
- Change From Baseline in UPDRS Part 3 (1 Hour Post-dose)(Baseline (predose Day 1) and 1 hour postdose at Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1(Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in UPDRS Part 4(Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12)
- Change From Baseline in UPDRS Part 3 (2 Hours Post-dose)(Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12)