A Clinical Study Investigating the Efficacy, Safety, Tolerability and Pharmacokinetics of ND0612H, a Solution of Levodopa/Carbidopa Administered as a Continuous Subcutaneous Infusion in Subjects With Advanced Parkinson's Disease

This phase IIa randomized, controlled, parallel-group study will be conducted in 36 subjects
with advanced PD who are treated with oral LD/CD at a stable dose and have predictable
morning "OFF" periods and at least 2.5 hrs of daily "OFF" periods. The study will
investigate the efficacy, PK, safety and tolerability of continuous SC infusion of 2 dosing
regimens of ND0612H. Regimen 1 will employ continuous infusion for 24 hrs using a low
infusion rate at night and a higher rate at daytime with supplemental administration of oral
immediate release (IR) LD/CD in the mornings. During the inpatient period of about 3 days,
the site staff will manage the administration and replacement of the infusions. On Day 4
subjects will be discharged home after they and their study partners have received training
on the administration of the infusion. A safety visit will be performed 4 weeks after the
last SC administration of the study drug.

Inclusion Criteria:

1. Male and female PD subjects of any race aged 30 to 80 years who sign an Institutional
Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).

2. PD diagnosis consistent with the UK Brain Bank Criteria.

3. Modified Hoehn & Yahr scale in "ON" state of stage ≤3.

4. Taking at least 4 doses/day of LD (or at least 3 doses/day of Rytary) and taking, or
have attempted to take, at least 2 other classes of anti-PD medications in a
therapeutic dose for at least 30 consecutive days each.

5. Subjects must be stable on their anti-PD medications for at least 30 days before Day
1.

6. Subjects may have had prior exposure to SC apomorphine injections/infusion but must
have stopped administration at least 4 weeks before the screening visit. Treatment
with apomorphine is prohibited during the entire ND0612H treatment period.

7. Must have a minimum of 2.5 hrs of "OFF" time per day with predictable early morning
"OFF" periods as estimated by the subject.

8. Must have predictable and well defined early morning "OFF" periods with a good
response to LD for treatment of the early morning "OFF" in the judgement of the
investigator.

9. Mini Mental State Examination (MMSE) score >26.

10. No clinically significant medical, psychiatric or laboratory abnormalities which the
investigator judges would be unsafe or non-compliant in the study.

11. Female subjects must be surgically sterile, postmenopausal (defined as cessation of
menses for at least 1 year), or willing to practice a highly effective method of
contraception. All female participants must be non-lactating and non-pregnant and
have a negative urine pregnancy test at Screening and at Baseline. Female subjects of
childbearing potential must practice a highly effective method of contraception
(e.g., oral contraceptives, a barrier method of birth control [e.g., condoms with
contraceptive foams, diaphragms with contraceptive jelly], intrauterine devices,
partner with vasectomy), 1 month before enrollment, for the duration of the study,
and 3 months after the last dose of study drug.

12. Willingness and ability to comply with study requirements

Exclusion Criteria:

1. Atypical or secondary parkinsonism.

2. Acute psychosis or hallucinations in past 6 months.

3. Any relevant medical, surgical, or psychiatric condition, laboratory value, or
concomitant medication which, in the opinion of the Investigator or the eligibility
reviewer, makes the subject unsuitable for study entry or potentially unable to
complete all aspects of the study.

4. Prior neurosurgical procedure for PD, or duodopa treatment.

5. Subjects with a history of drug abuse or alcoholism within the past 12 months.

6. Clinically significant ECG rhythm abnormalities.

7. Renal or liver dysfunction that may alter drug metabolism including: serum creatinine
>1.3 mg/dL, serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
>2 x upper limit of normal (ULN), total serum bilirubin >2.5 mg/dL.

8. Subjects who are not willing to operate the pump system.