A Phase 3, 40‑Week, Active‑Controlled, Double‑Blind, Double‑Dummy Extension Study of Preladenant in Subjects With Moderate to Severe Parkinsons Disease
试验速览
- 阶段
- 3 期
- 状态
- Other
- 入组人数
- 750
- 试验地点
- 7
- 主要终点
- 2. Incidence of diastolic blood pressure (DBP) ≥ 105 mm Hg
研究概览
简要总结
The purpose of this trial is to assess safety data collected for up to 52 weeks (from the beginning of P04938 or P07037 to the end of P06153) and to characterize the efficacy of preladenant over the same time period in participants with moderate to severe Parkinson’s disease (PD).
A Phase 3, 40-Week, Active-Controlled, Double-Blind, Double Dummy Extension Study of
Preladenant in Subjects With Moderate to Severe Parkinson’s Disease
Number of Trial Centers: Approximately 163 sites.
Duration of Participation: Each subject will participate for approximately 42 weeks in P06153 (ie, 40
weeks of active treatment followed by a 2-week Safety Follow-Up Visit).
Duration of Trial: The trial will require approximately 3 years from the beginning to the end of the
overall trial (first subject signing informed consent to last contact with last subject).
Preladenant is a tablet. Rasagiline will be supplied as a capsule. A placebo tablet matching preladen
will be available; and a placebo capsule matching rasagiline also will be available.
During the 40-week Treatment Period, subjects will receive one tablet and one capsule orally each
morning and one tablet orally each evening in a double-blind, double-dummy design
AUSTRIA
BRAZIL
BULGARIA
CANADA
CZECH REPUBLIC
FINLAND
FRANCE
GERMANY
INDIA
ISRAEL
ITALY
NETHERLANDS
PERU
POLAND
RUSSIA
SPAIN
TURKEY
UNITED KINGDOM
USA
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 30.00 Year(s) 至 85.00 Year(s)（—）
- 性别
- All
入选标准
- •Participants who have completed the 12-week treatment period of the parent trial, P04938 or P
- •Participants must be willing and able to provide written informed consent for P
- •Participants must be able to adhere to dose and visit schedules.
- •Participants must be taking levo-dopa (L-dopa).
- •Participants may be taking additional adjunct PD medications (e.g., dopamine agonists, entacapone).
- •Each participant must have results of clinical laboratory tests (hematology, blood chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator as evidenced by the last available test results from the parent study (P04938 or P07037), and no results fall within the parameters for exclusion described below in the exclusion criterion for liver-related findings.
- •There has been no change in, or there has been no finding to warrant checking, serology status (for cytomegalovirus [CMV], Epstein-Barr virus [EBV], and Hepatitis B, C, and E).
- •Each participant must have results of a physical examination within normal limits, including blood pressure, within normal limits or clinically acceptable limits to the investigator, and not within the parameters for exclusion described below in the exclusion criterion for blood pressure.
- •All participants who are sexually active or plan to be sexually active agree to use a highly effective method of birth control while the participant is in the study and for 2 weeks after the last dose of study drug. A male participant must not donate sperm within 2 weeks after the last dose of study drug.
排除标准
- •Exclusion Criteria:.
- •Any participant who discontinued from P04938 or P07037 for any reason.
- •Any participant with a severe or ongoing unstable medical condition (e.g. any form of clinically significant cardiac disease symptomatic orthostatic hypotension seizures or alcohol/drug dependence).
- •Any participant with a history of poorly controlled diabetes (e.g. HbA1c greater than 8.5) or significantly abnormal renal function (e.g. creatinine greater than 2.0 mg/dL) in the opinion of the investigator.
- •As a continuation of the liver-related withdrawal criteria from the parent studies (P04938 and P07037) any participant with elevated values for alanine aminotransferase (ALT) aspartate aminotransferase (AST) or total bilirubin (T BIL) as evidenced by the most recent chemistry panel results in the parent study meeting any one of the following criteria:.
- •ALT or AST greater than 8 x upper limit of normal (ULN).
- •ALT or AST greater than 3 x ULN and (T-BIL greater than 2 x ULN or international normalized ratio [INR] greater than 1.5 that is not due to anti-coagulation) at the same visit.
- •ALT or AST greater than 3 x ULN with the appearance of worsening fatigue nausea vomiting right upper quadrant pain or tenderness fever rash and/or eosinophilia (greater than 5%).
- •As a continuation of the blood pressure (BP) withdrawal criteria from the parent study (P04938 or P07037) any participant meeting the following criteria for the second of two consecutive visits separated by 7 days (i.e. the participant met one of the BP criteria once already 7 days before the P06153 screening visit):.
- •Systolic BP greater than or equal to 180 mm Hg or diastolic BP greater than or equal to 105 mm Hg or.
- •An elevation from baseline BP in the parent study (P04938 or P07037) of systolic BP greater than or equal to 40 mm Hg or diastolic BP greater than or equal to 20 mm Hg.
- •A participant must not have a history within the past 5 years of a primary or recurrent malignant disease with the exception of adequately treated basal cell or squamous cell skin cancer in situ cervical cancer or in situ prostate cancer with a normal prostate-specific antigen (PSA) post resection.
- •Any participant with an average daily consumption of more than three 4-ounce glasses (118 mL) of wine or the equivalent.
- •A participant must not have received certain prespecified medications or ingested high tyramine-containing aged cheeses (e.g. Stilton) for a prespecified time window before the trial during the trial and for 2 weeks after the trial.
- •Any participant with allergy/sensitivity to the investigational products or their excipients.
- •Any female participant breast feeding or considering breast feeding.
- •Any female participant pregnant or intending to become pregnant.
- •Any participant with any clinically significant condition or situation other than the condition being studied that in the opinion of the investigator would interfere with the trial evaluations or optimal participation in the trial.
- •Any participant with a member or a family member of the personnel of the investigational or sponsor staff directly involved with this trial.
结局指标
主要结局
2. Incidence of diastolic blood pressure (DBP) ≥ 105 mm Hg
时间窗: 1.Up to 42 weeks from the beginning of P06153 | 2.Up to 42 weeks from the beginning of P06153 | 3.Up to 42 weeks from the beginning of P06153 | 4.Up to 42 weeks from the beginning of P06153 | 5.Up to 40 weeks from the beginning of P06153 | 6.Screening and 40 weeks from the beginning of P06153
1. Incidence of systolic blood pressure (SBP) ≥ 180 mm Hg
时间窗: 1.Up to 42 weeks from the beginning of P06153 | 2.Up to 42 weeks from the beginning of P06153 | 3.Up to 42 weeks from the beginning of P06153 | 4.Up to 42 weeks from the beginning of P06153 | 5.Up to 40 weeks from the beginning of P06153 | 6.Screening and 40 weeks from the beginning of P06153
5. Columbia Suicide Severity Rating Scale (CSSRS): Suicidality, Suicidal Behavior, Suicidal Ideation
时间窗: 1.Up to 42 weeks from the beginning of P06153 | 2.Up to 42 weeks from the beginning of P06153 | 3.Up to 42 weeks from the beginning of P06153 | 4.Up to 42 weeks from the beginning of P06153 | 5.Up to 40 weeks from the beginning of P06153 | 6.Screening and 40 weeks from the beginning of P06153
3. Incidence of alanine aminotransferase (ALT) ≥ 3 x upper limit of normal and with a ≥10% increase from baseline
时间窗: 1.Up to 42 weeks from the beginning of P06153 | 2.Up to 42 weeks from the beginning of P06153 | 3.Up to 42 weeks from the beginning of P06153 | 4.Up to 42 weeks from the beginning of P06153 | 5.Up to 40 weeks from the beginning of P06153 | 6.Screening and 40 weeks from the beginning of P06153
6. Epworth Sleepiness Scale Score
时间窗: 1.Up to 42 weeks from the beginning of P06153 | 2.Up to 42 weeks from the beginning of P06153 | 3.Up to 42 weeks from the beginning of P06153 | 4.Up to 42 weeks from the beginning of P06153 | 5.Up to 40 weeks from the beginning of P06153 | 6.Screening and 40 weeks from the beginning of P06153
4. Incidence of aspartate aminotransferase (AST) ≥ 3 x upper limit of normal and with a ≥10% increase from baseline
时间窗: 1.Up to 42 weeks from the beginning of P06153 | 2.Up to 42 weeks from the beginning of P06153 | 3.Up to 42 weeks from the beginning of P06153 | 4.Up to 42 weeks from the beginning of P06153 | 5.Up to 40 weeks from the beginning of P06153 | 6.Screening and 40 weeks from the beginning of P06153
次要结局
- To characterize the long-term efficacy of preladenant in subjects with(moderate to severe PD.)