An Active-Controlled Extension Study to NCT01155466 [P04938] and NCT01227265 [P07037] (P06153)
Condition: Parkinson Disease; Idiopathic Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: Preladenant; Rasagiline; Placebo to preladenant; Placebo to rasagiline
Intervention description: Daily for 40 weeks: 2, 5, or 10 mg preladenant tablet each morning; 2, 5, or 10 mg preladenant tablet each evening (approximately 8 hours after the morning dose); Daily for 40 weeks: 1 mg rasagiline capsule each morning; Placebo to match preladenant given daily for 40 weeks: placebo tablet each morning; placebo tablet each evening (approximately 8 hours after the morning dose); Placebo to match rasagiline given daily for 40 weeks: placebo capsule each morning
Intervention MeSH terms: Rasagiline
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 839.0
Sex: All
Minimum age: 30 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      The primary purpose of this extension study is to assess the long-term safety and
      tolerability of preladenant in participants from parent studies NCT01155466 [P04938] and
      NCT01227265 [P07037] with moderate to severe Parkinson's Disease (PD). The study will also
      characterize the long-term efficacy of preladenant in participants with PD.

      Participants will continue to receive their stable regimen of levodopa (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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants who have completed the 12-week treatment period of the parent trial,
             P04938 or P07037.

          -  Participants must be willing and able to provide written informed consent for P06153.

          -  Participants must be able to adhere to dose and visit schedules.

          -  Participants must be taking 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.

        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., hemoglobin A1c >
             8.5) or significantly abnormal renal function (e.g., creatinine > 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 > 8 x upper limit of normal (ULN).

          -  ALT or AST > 5 x ULN for more than 2 weeks.

          -  ALT or AST > 3 x ULN and (T-BIL > 2 x ULN or international normalized ratio [INR] >
             1.5 that is not due to anti-coagulation) at the same visit.

          -  ALT or AST > 3 x ULN with the appearance of worsening fatigue, nausea, vomiting, right
             upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 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 ≥ 180 mm Hg or diastolic BP ≥ 105 mm Hg, or

          -  An elevation from baseline BP in the parent study (P04938 or P07037) of systolic BP >=
             40 mm Hg or diastolic BP ≥ 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.