Study of Urate Elevation in Parkinson's Disease, Phase 3
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: Inosine; Placebo
Intervention description: capsules containing 500 mg of inosine; capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 298.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: SURE-PD3; Parkinson's disease; PD; Inosine; Urate; Parkinson Study Group (PSG)

Summary:

      A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial to determine
      whether oral inosine dosed to moderately elevate serum urate (from ≤5.7 mg/dL to 7.1-8.0
      mg/dL) over 2 years slows clinical decline in early PD.

      Clinical decline will be assessed as change in the primary outcome variable of the Movement
      Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), a composite scale
      comprising patient- and clinician-reported outcomes.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        Study subjects meeting all of the following criteria will be allowed to enroll in the
        study:

          1. Willingness and ability to give written informed consent and to comply with trial
             procedures.

          2. Fulfillment of diagnostic criteria for idiopathic PD with at least two of the cardinal
             signs of PD (resting tremor, bradykinesia, rigidity) present at 2nd screening and
             baseline evaluations, as assessed by the Site Investigator.

          3. Absence of current or imminent (within 90 days of enrollment) PD disability requiring
             dopaminergic therapy, as assessed by the Site Investigator.

          4. Modified Hoehn and Yahr Scale Stage 1 to 2.5 inclusive.

          5. Age 30 or older at the time of PD diagnosis.

          6. Diagnosis of PD made within 3 years prior to 1st Screening Visit.

          7. Non-fasting serum urate ≤ 5.7 mg/dL at 1st Screening Visit (SC1).

          8. If the subject is female, then:

               1. Being surgically sterile (hysterectomy or tubal ligation), or

               2. Being postmenopausal (last menstruation was two years or more prior to 2nd
                  Screening Visit), or

               3. For those of childbearing potential

                    -  Using a reliable form of contraception for 60 days or more prior to Baseline
                       Visit and agreeing to continue such use for 30 days post last dose of study
                       drug. Reliable forms of contraception include: abstinence; implanted,
                       injected or oral contraceptives (birth control pills), intrauterine device
                       in place for at least 3 months prior to Baseline Visit, vaginal ring with
                       spermicide, barrier with spermicide such as male or female condom, diaphragm
                       or cervical cap, transdermal patch; male partner with vasectomy.

                    -  And having a negative pregnancy test at the 2nd Screening Visit. [Note that
                       a urine pregnancy test will be performed at screening on all women who are
                       not at least two years postmenopausal or surgically sterile.]

        EXCLUSION CRITERIA:

        Study subjects meeting any of the following criteria during screening evaluations will be
        excluded from entry into the study:

          1. Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis,
             cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative
             disease.

          2. Dopamine transporter (DAT) brain scan without evidence of dopamine deficit.

          3. History of gout.

          4. History of uric acid or urate urolithiasis, or recurrent urolithiasis all of unknown
             type.

          5. A screening test positive for uric acid crystalluria, urine pH ≤ 5.0, or an estimated
             glomerular filtration rate < 60 ml/min/1.73 m2.

          6. History of myocardial infarction or stroke.

          7. Symptomatic congestive heart failure with a documented ejection fraction below 45%.

          8. History of severe chronic obstructive pulmonary disease.

          9. Mini Mental State Exam score < 25; i.e., a score of 0 to 24.

         10. Use of any anti-parkinsonian medication (including levodopa, dopamine agonists,
             amantadine, entacapone and the anticholinergic agents trihexyphenidyl and benztropine)
             other than monoamine oxidase-B inhibitors within 60 days of Baseline, or in excess of
             90 days.

         11. Change in the dosage of (or initiation of) a monoamine oxidase-B (MAO-B) inhibitor
             within 90 days prior to Baseline, i.e., entry on a MAO-B inhibitor requires a stable
             dosage for the 90 days prior to Baseline.

         12. Use of the following within 30 days prior to the Baseline Visit: inosine, allopurinol,
             febuxostat, probenecid, more than 50 IU of vitamin E daily, or more than 300 mg of
             vitamin C daily (though a daily standard multivitamin such as Bayer One-A-Day® or
             Centrum® is permissible), reserpine, methylphenidate, amphetamines, cinnarizine,
             monoamine oxidase-A inhibitors, tetrabenazine, neuroleptics or other dopamine blocking
             drugs.

         13. Use of the following within 90 days prior to the DAT neuroimaging screening
             evaluation: modafinil, armodafinil, metoclopramide, alpha-methyldopa, methylphenidate,
             reserpine, or amphetamine derivative.

         14. Unstable dosing of a thiazide -- such as hydrochlorothiazide (e.g., Esidrex),
             chlorothiazide (e.g., Diuril), chlorthalidone (e.g., Hygroton), indapamide (e.g.,
             Lozol), metolazone (e.g., Zaroxolyn), which are permissible as long as the subject is
             on a stable dose from 1 week prior to the 1st Screening Visit through the Baseline
             Visit.

         15. Known unstable medical or psychiatric condition that may compromise participation in
             the study. (Note that difficulty swallowing large capsules might preclude
             participation due to the size of the study drug capsules.)

         16. Clinically serious abnormality in the screening visit laboratory studies or ECG, as
             determined by the Site Investigator.

         17. Participation in another investigational treatment study within 30 days prior to the
             Baseline Visit.

         18. Known hypersensitivity or intolerability to inosine.

         19. Known hypersensitivity to DaTscan (either the active substance of ioflupane I-123 or
             to any of the excipients).