A Clinical Study of Efficacy, Safety, Tolerability and PK of ND0612H in Subjects With Advanced Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: ND0612 (Levodopa/Carbidopa solution); ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD
Intervention description: The total daily dose of levodopa/carbidopa 720/90 mg. Device: CRONO TWIN pump system.; The total daily dose levodopa/carbidopa from ND0612 538/67 mg. Morning dose of oral IR-LD/CD 150/15 mg. Device: CRONO TWIN pump system.
Intervention MeSH terms: Levodopa; Carbidopa; Pharmaceutical Solutions
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 38.0
Sex: All
Minimum age: 30 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This is a multicenter, parallel-group, rater-blinded, randomized clinical study in subjects
      with advanced PD investigating the efficacy, PK, safety and tolerability of continuous SC
      infusion of 2 dosing regimens of ND0612H, a solution of LD/CD delivered via a pump system as
      a continuous SC infusion, compared to standard oral LD/CD. After screening, subjects will
      undergo 1 day of standard oral LD/CD inpatient dosing followed by 2 days of inpatient
      treatment with 1 of 2 randomly allocated (1:1 randomization ratio) dosing regimens of ND0612H
      continuous SC infusion. Subjects will then continue on a maintenance dose of the assigned
      ND0612H dosing regimen for the next 25 days. A safety visit will be performed 4 weeks after
      the last SC administration of the study drug for a total of about 2.5 months of participation
      for each subject enrolled into the trial.
    

Eligibility criteria:

        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.