Study of Urate Elevation in Parkinson's Disease, Phase 3

Capsules containing 500 mg of inosine (active drug) or ~500 mg of lactose (placebo) will be
taken orally up to two capsules three times per day (i.e., up to 3 g/day) for 24 months. In
the inosine-treated group the number of capsules taken per day will be titrated to serum
urate levels - measured at trough at study visits no more than three months apart - in order
to achieve concentrations of 7.1-8.0 mg/dL. Initial dosing will be tailored to individualized
factors including gender and pretreatment serum urate, and then advanced gradually toward the
projected target dose. Adjustments in dosing of placebo capsules in the control arm will be
algorithm-based to match dosing of inosine capsules in the active drug arm.

Following study drug discontinuation all subjects will be followed during a 3-month wash-out
period by telephone calls and a final study visit. All study visits after screening will
include measurement of the primary outcome variable (MDS-UPDRS) and most will include
secondary outcome variables: adverse events, dose adjustments, disability warranting
initiation of dopaminergic therapy, Quality of Life in Neurological Disorders (Neuro-QOL),
39-item Parkinson's Disease Questionnaire (PDQ-39), Schwab & England Activities of Daily
Living (S&E ADL) scale, Montreal Cognitive Assessment (MoCA), and orthostatic vital signs.

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).