Placebo Controlled Study of Preladenant in Participants With Moderate to Severe Parkinson's Disease (P07037)
Condition: Parkinson Disease; Idiopathic Parkinson Disease; Idiopathic Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: Preladenant; Placebo
Intervention description: Preladenant 2 mg or 5 mg oral tablet taken twice daily; Preladenant-matching placebo oral tablet taken twice daily
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 476.0
Sex: All
Minimum age: 30 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This is a study of the efficacy and safety of preladenant in adult participants with moderate
      to severe Parkinson's Disease (PD). While on this study, participants will continue to take
      their usual, prescribed, stable regimen of levodopa (L-dopa) or L-dopa plus adjunct PD
      medications and will be randomized to receive 2 mg preladenant, 5 mg preladenant, or placebo,
      twice daily, for 12 weeks. After that, participants may choose to receive additional
      treatment with preladenant. The primary hypothesis is that at least the 5 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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Each participant must have a diagnosis of idiopathic Parkinson's disease.

          -  Each participant 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.

          -  Each participant 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 agonist, anticholinergics) are permitted to enroll
             in this trial. Participants taking only L-dopa are permitted to enroll in this trial.

          -  Each participant 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.

          -  Each participant, with or without the help of a caregiver, must be capable of
             maintaining an accurate and complete symptom diary and to adhere to dose and visit
             schedules.

          -  Each participant must 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 (below).

          -  All participants who are 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. A male participant must also not donate sperm within 2 weeks
             after the last dose of study drug.

        Exclusion Criteria:

          -  A participant 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 exposure to a known neurotoxin, or
             any neurological features not consistent with the diagnosis of PD as assessed by the
             investigator.

          -  A participant must not have a history of repeated strokes 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.

          -  A participant must not have had surgery for their PD.

          -  A participant must not be at imminent risk of self-harm or harm to others.

          -  A participant must not have a systolic blood pressure (BP) ≥150 mm Hg OR diastolic BP
             ≥95 mm Hg at Screening and at 2 BP rechecks prior to study start.

          -  A participant 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 a participant must not
             have heart failure staged New York Heart Association Class III or IV.

          -  A participant must not have an alanine aminotransferase (ALT) or aspartate
             aminotransferase (AST) ≥3 x the upper limit of normal (ULN) or total bilirubin (T BIL)
             ≥1.5 x ULN.

          -  A participant must not have a history of 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.

          -  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.

          -  A participant must not have received certain prespecified medications for a
             prespecified time window before the trial.

          -  A participant must not have an average daily consumption of more than three 4 ounce
             glasses (118 mL) of wine or the equivalent.

          -  A participant 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).

          -  A participant must not have allergy/sensitivity to investigational product(s) or
             its/their excipients.

          -  A participant must not be breast-feeding, considering breast-feeding, pregnant, or
             intending to become pregnant.

          -  A participant must not have used preladenant ever, or any investigational drugs within
             90 days immediately before Screening.