A Long Term Safety Study of ND0612 Administered as a Continuous SC Infusion in Advanced Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: ND0612
Intervention description: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 214.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      This is a multi-center, international, open-label, safety study of ND0612, a solution of
      levodopa/carbidopa (LD/CD) delivered via a pump system as a continuous SC infusion in
      subjects with advanced Parkinson's Disease (PD).
    

Eligibility criteria:

        INCLUSION CRITERIA:

        Cohort 1.

          1. Subject is able to, and has signed an Institutional Review Board/Ethics Committee
             (IRB/EC)-approved informed consent form (ICF).

          2. Subject has completed the treatment period of study ND0612H-006 not more than one
             month prior to enrolling in ND0612H-012.

          3. Willing and able to administer the SC infusion alone or with the assistance of a study
             partner and able to comply with the study specific procedures.

        Cohort 2.

          1. Male and female PD subjects of any race aged at least 30 years who sign an
             IRB/EC-approved 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/DDI (or at least 3 doses/day of Rytary) and taking,
             or have attempted to take, at least one other PD treatment for at least 30 days.

          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 continuous apomorphine administration at least 4 weeks before the
             screening visit. Treatment with apomorphine is prohibited during the entire ND0612
             treatment period.

          7. Must have a minimum of 2 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 (hysterectomy, bilateral oophorectomy, or
             tubal ligation), 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,
             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. Alternatively,
             true abstinence is acceptable when it is in line with the subject's preferred and
             usual lifestyle. If a subject is usually not sexually active but becomes active, the
             subject and sexual partner must comply with the contraceptive requirements detailed
             above.

         12. Willing and able to administer the SC infusion alone or with the assistance of a study
             partner after a screening period of up to 40 days and willing and able to comply with
             study requirements.

         13. Subjects should have a named study partner.

        EXCLUSION CRITERIA:

        Cohort 1 and 2. Previously unable to tolerate ND0612 and/or have experienced intolerable
        adverse drug reactions associated with its use, regardless of the dosing regimen
        administered.

        Cohort 2.

          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 makes the subject
             unsuitable for study entry or potentially unable to complete all aspects of the study.

          4. Any malignancy in the 5 years prior to randomization (excluding basal cell carcinoma
             of the skin or cervical carcinoma in situ that have been successfully treated).

          5. Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human
             Immunodeficiency Virus (HIV) at the Screening visit.

          6. Prior neurosurgical procedure for PD, or Duodopa treatment

          7. Subjects with a history of drug abuse or alcoholism within the past 12 months.

          8. Clinically significant ECG rhythm abnormalities.

          9. 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.

         10. Current participation in a clinical trial with an investigational product or past
             participation within the last 30 days before Day 1.