A Placebo- and Active-Controlled Study of Preladenant in Early Parkinson's Disease (PD) (P05664)
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: Preladenant 2 mg tablet; Preladenant 5 mg tablet; Preladenant 10 mg tablet; Rasagiline 1 mg capsule; Placebo for Rasagiline 1 mg capsule; Placebo for Preladenant
Intervention description: Preladenant 2 mg oral tablet taken twice daily; Preladenant 5 mg oral tablet taken twice daily; Preladenant 10 mg oral tablet taken twice daily; Rasagiline 1 mg oral capsule taken once daily; Placebo for rasagiline 1 mg oral capsule taken once daily; Placebo for preladenant 2 mg, 5 mg, or 10 mg oral tablet taken twice daily
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: 1022.0
Sex: All
Minimum age: 30 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This is a one year, 2-part study to determine the efficacy and safety of preladenant, an
      adenosine type 2a (A2a) receptor antagonist. The purpose of Part 1 (first 26 weeks) is to
      determine if preladenant is effective in the treatment of early Parkinson's Disease. The
      purpose of Part 2 (second 26 weeks) is to determine if preladenant is safe and well
      tolerated. The primary efficacy hypothesis is that at least the 10 mg twice daily dose of
      preladenant is superior to placebo as measured by the change from Baseline to Week 26 in the
      sum of Unified Parkinson's Disease Rating Scale (UPDRS) Parts 2 and 3 scores (UPDRS2+3).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a diagnosis of idiopathic PD for < 5 years.

          -  If receiving amantadine and/or anticholinergics, must have been on a stable regimen of
             treatment for at least the 5 weeks immediately before Screening. (Note: Participants
             who are not taking any medications for PD are permitted to enroll in this trial.)

          -  Must have a UPDRS Part 3 score of ≥10, a Hoehn and Yahr Stage ≤3, be ≥30 to ≤85 years
             of age, and have results of Screening clinical laboratory tests drawn within 5 weeks
             prior to randomization, clinically acceptable to the investigator, and not within the
             parameters specified for exclusion.

          -  If sexually active or plan to be sexually active, must 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 also not donate sperm during the
             trial and within 2 weeks after the last dose of study drug.

        Exclusion Criteria:

          -  Must not have a form of drug-induced or atypical Parkinsonism, cognitive impairment
             (ie, Montreal Cognitive Assessment [MoCA] score <22), 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 had surgery for PD.

          -  Must not have a history of repeated strokes with stepwise progression of Parkinsonism
             or head injuries, or a stroke within 6 months of screening; poorly controlled
             diabetes; abnormal renal function; or a severe or ongoing unstable medical condition.

          -  Must not have failed to show a therapeutic response if a diagnostic levodopa (L dopa)
             challenge had been done with a large test dose (>500 mg) of L dopa (if malabsorption
             excluded), or failed to respond to an adequate previous treatment with dopaminergic
             therapy.

          -  Must not have been treated with L dopa or dopamine agonists for 30 days or more. A
             participant who has been treated with L-dopa or dopamine agonists for <30 days will be
             allowed to enter the study. These participants must stop taking dopaminergic
             medication 30 days prior to Randomization.

          -  Must not be at imminent risk of self-harm or harm to others.

          -  Must not have elevated blood pressure (BP) (systolic BP ≥150 mm Hg or diastolic BP ≥95
             mm Hg) that cannot be adequately controlled with antihypertensive medication, as
             demonstrated by 2 BP measurements meeting acceptable BP criterion at consecutive
             scheduled or unscheduled visits between Screening and Randomization (a 5-6 week
             period), one of which must be the Randomization visit.

          -  Must not have had any clinically significant cardiovascular event or procedure for 6
             months prior to Randomization, including, but not limited to, myocardial infarction,
             angioplasty, unstable angina, or heart failure; and a participant 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 active serologically-confirmed hepatic dysfunction (defined as viral
             infection [Hepatitis B, C, or E; Epstein-Barr virus (EBV)]; cytomegalovirus [CMV] or a
             history of diagnosis of drug- or alcohol-induced hepatic toxicity or frank hepatitis,
             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.

          -  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.