A Phase 2, 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Assess the Efficacy and Safety of Preladenant in Japanese Subjects With Moderate to Severe Parkinson's Disease. (Phase 2; Protocol No. P06402)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 450
- 主要终点
- Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12
研究概览
简要总结
This study is to evaluate the efficacy of a range of preladenant doses compared with placebo in participants with moderate to severe Parkinson's disease (PD) experiencing motor fluctuations and receiving a stable dose of levodopa (L-dopa), as measured by "off" time. Participants will continue to receive their stable regimen of L-dopa plus any adjunct medications during the study as prescribed by their physician. Several classes of adjunct medications may be used, including Amantadine, anticholinergics, dopa decarboxylase inhibitors, and dopamine agonists.
Primary Hypothesis: At least the 10 mg twice daily dose of preladenant is superior to placebo as measured by the change from Baseline to Week 12 in the mean "off" time.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have a diagnosis of idiopathic PD based on the United Kingdom Parkinson's Disease Society Brain Bank Criteria, judged to be moderate to severe
- •Must have received prior therapy with L-dopa for more than 1 year before Screening
- •Must have been on a stable, optimal dopaminergic treatment regimen, defined as maximum
- •therapeutic effect achieved with available anti-Parkinsonian treatment, for at least the 4 weeks immediately before randomization
- •If receiving one or more of the following adjunctive treatments: amantadine, anticholinergics, catechol-O-methyltransferase inhibitors, dopa decarboxylase inhibitors, dopamine agonists, entacapone, L-dopa, must have been on a stable regimen of treatment for at least the 4 weeks immediately before randomization
- •Hoehn and Yahr stage must be ≥ 2.5 and ≤ 4 following optimum titration of treatment medications at Screening
- •Must be experiencing motor fluctuations with or without dyskinesias following optimum titration of
- •treatment medications and within the 4 weeks immediately before Screening
- •Must be experiencing a minimum of 2 hours/day of "off" time as estimated by the investigator
- •and supported by the symptom diary (Daily Diary) at the Diary Training Visit
- •With or without the help of a caregiver, must be capable of maintaining an accurate and
- •complete symptom diary (Daily Diary) as assessed at the Diary Training Visit
- •Must have results of Screening clinical laboratory tests (complete blood count [CBC], blood
- •chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator at Screening
- •Must have results of a physical examination within normal limits or clinically acceptable limits
- •to the investigator
- •Must be able to adhere to dose and visit schedules
- •Females of child-bearing potential must have a negative serum pregnancy test (human chorionic
- •gonadotropin [hCG]) at Screening and must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for 2 weeks after stopping the medication
排除标准
- •Must not have a form of drug-induced or atypical parkinsonism, cognitive impairment, bipolar disorder, schizophrenia, or other psychotic disorder
- •Must not have had surgery for PD
- •Must not have an untreated major depressive disorder meeting Diagnostic and Statistical Manual
- •of Mental Disorders IV Text Revision (DSM-IV-TR) criteria
- •Must not be at imminent risk of self-harm or harm to others, in the investigator's opinion based on
- •clinical interview
- •Must not have participated in any studies using preladenant
- •Must not have allergy/sensitivity to preladenant or any of its excipients
- •Must not have used any investigational drugs or participated in any other clinical trial within 90 days of Screening
研究组 & 干预措施
Preladenant 2 mg
Participants will receive preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks.
干预措施: Preladenant (Drug)
Preladenant 5 mg
Participants will receive preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
干预措施: Preladenant (Drug)
Preladenant 10 mg
Participants will receive preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
干预措施: Preladenant (Drug)
Placebo
Participants will receive a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
干预措施: Placebo tablet to match Preladenant (Drug)
结局指标
主要结局
Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12
时间窗: Baseline and Week 12
The "on" state is defined as the period of time during which a participant's symptoms of PD improve or disappear following treatment with levodopa (L-dopa) or dopamine agonists. The "off" state is defined as the period of time characterized by the return of symptoms (i..e. tremor, slowness, and rigidity) following treatment with L-dopa or dopamine agonists. Study participants reported their symptoms at half-hour intervals as "off", "on", or "asleep" on their daily diary for 3 days before randomization (baseline) and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "off" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects, and an unstructured covariance matrix was used to model the correlation among repeated measurements.
Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to 14 weeks
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to 12 Weeks
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
次要结局
- Percentage of Participants With ≥30% Reduction in "Off" Time at Week 12(Up to 12 Weeks)
- Change From Baseline in Mean "On" Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12(Baseline and Week 12)