A Placebo- and Active Controlled Study of Preladenant in Subjects With Moderate to Severe Parkinson's Disease (P04938)
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: Preladenant 2 mg tablet; Preladenant 5 mg tablet; Preladenant 10 mg tablet; Placebo to Preladenant Tablet; Rasagiline 1 mg capsule; Placebo to Rasagiline capsule
Intervention description: one 2 mg tablet orally twice daily; one 5 mg tablet orally twice daily; one 10 mg tablet orally twice daily; one tablet orally twice daily; one 1 mg capsule orally in AM; one capsule orally in AM
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: 778.0
Sex: All
Minimum age: 30 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Idiopathic Parkinson Disease; Idiopathic Parkinson's Disease

Summary:

      When a patient with Parkinson's disease (PD) is initially treated with L-dopa or dopamine
      agonists, the symptoms of PD improve or disappear. After several years of taking L dopa or
      dopamine agonists, patients notice that their PD medications wear off sooner than when they
      first started taking them. This "wearing off" is characterized by the return of symptoms
      (i.e., tremor, slowness, and rigidity) and may occur over the course of a few minutes to an
      hour. When a patient's PD symptoms have returned, the patient is said to be in the "off"
      state. When the patient takes another dose of medication, and his/her PD symptoms improve or
      resolve, the patient is said to be in the "on" state. Antagonism of adenosine Type 2a
      receptors (A2a) may provide relief of PD symptoms. This trial will test the hypothesis that
      A2a receptor antagonism can lead to improvement in the function of PD participants taking a
      stable dose of L-dopa, as measured by a reduction in "off" time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have a diagnosis of moderate to severe idiopathic Parkinson's disease.

          -  Must have received prior therapy with L dopa for approximately 1 or more years
             immediately before Screening and must continue to have a beneficial clinical response
             to L dopa

          -  Must have been on a stable dopaminergic treatment regimen for at least the 5 weeks
             immediately before Randomization. Participants receiving other adjunctive treatments
             (eg, dopamine agonists, anticholinergics, entacapone) or taking only L dopa are
             permitted, provided the treatment regimen has been taken for at least 5 weeks prior to
             randomization

          -  Must be experiencing motor fluctuations with or without dyskinesias within the 4 weeks
             immediately before Screening, must be experiencing a minimum of 2 hours/day of "off"
             time, and have a Hoehn & Yahr stage between 2.5 and 4 when in the "on" state

          -  Must be capable of maintaining an accurate and complete symptom diary and to adhere to
             dose and visit schedules with or without the help of a caregiver

          -  Must have results of a physical examination and screening clinical laboratory tests
             clinically acceptable to the investigator

          -  If sexually active or plan to be sexually active agree to use a highly effective
             method of birth control while in the study and for 2 weeks after the last dose of
             study drug. Males must also not donate sperm during the trial within 2 weeks after the
             last dose of study drug

        Exclusion Criteria:

          -  Must not have a form of drug induced or atypical parkinsonism, a cognitive impairment,
             bipolar disorder, untreated major depressive disorder, schizophrenia, or other
             psychotic disorder; history of exposure to a known neurotoxin, or any neurological
             features not consistent with the diagnosis of PD as assessed by the investigator

          -  Must not have a history of repeated strokes or head injuries, or a stroke within 6
             months of Screening

          -  Must not have poorly-controlled diabetes or abnormal renal function

          -  Must not have had surgery for their PD

          -  Must not be at imminent risk of self-harm or harm to others

          -  Must not have sleep attacks or compulsive behavior that would interfere with the
             integrity of the trial or would pose a risk to the subject in participating in the
             trial

          -  Must not have a systolic blood pressure (BP) ≥150 mm Hg OR diastolic BP ≥95 mm Hg at
             Screening

          -  Must not have had any clinically significant cardiovascular event or procedure for 6
             months prior to study start, including, but not limited to, myocardial infarction,
             angioplasty, unstable angina, or heart failure; and must not have heart failure staged
             New York Heart Association Class III or IV

          -  Must not have an alanine aminotransferase (ALT) or aspartate amino transferase (AST)
             ≥3 x the upper limit of normal (ULN) or total bilirubin (T-BIL) ≥1.5 x ULN

          -  Must not have a history of serologically confirmed hepatic dysfunction (defined as
             viral infection [Hepatitis B or C; Epstein Barr virus (EBV); cytomegalovirus (CMV)])
             or a history of diagnosis of drug or alcohol induced hepatic toxicity or frank
             hepatitis

          -  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

          -  Must not have received certain prespecified medications or ingested high
             tyramine-containing aged cheeses (eg, Stilton) for a prespecified time window before
             the trial, during the trial, and for 2 weeks after the trial

          -  Must not have an average daily consumption of more than three 4 ounce glasses (118 mL)
             of wine or the equivalent

          -  Must not have a severe or ongoing unstable medical condition (eg, any form of
             clinically significant cardiac disease, symptomatic orthostatic hypotension, seizures,
             or alcohol/drug dependence)

          -  Must not have allergy/sensitivity to investigational product(s) or its/their
             excipients

          -  A female subject must not be breast-feeding, considering breast-feeding, pregnant, or
             intending to become pregnant

          -  Must not have used preladenant ever, or any investigational drugs within 90 days
             immediately before Screening