Long-Term Safety Evaluation of Continuous Subcutaneous Infusion of ND0612 (Carbidopa/Levodopa) in Advanced Parkinson's Disease
- Trial ID
- 2024-513548-27-00
- Protocol
- ND0612H-012
- Sponsor
- Neuroderm Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the long-term **safety** and tolerability of ND0612, a solution of **levodopa/carbidopa** administered as a continuous subcutaneous infusion, in patients with advanced **Parkinson's disease**. This assessment is crucial for determining the viability of ND0612 as a sustained treatment option, potentially improving the management of motor symptoms and enhancing the quality of life for individuals with advanced Parkinson's disease.
Secondary objectives include:
- Further assessment of the safety and tolerability of ND0612, focusing on aspects such as suicidality, excessive daytime sleepiness, vital signs, laboratory tests, and electrocardiogram data.
- Evaluation of the long-term systemic and local safety and tolerability of the continuous subcutaneous infusion of ND0612.
Participants
The clinical trial involves a total of **172 participants** diagnosed with **Parkinson's disease**. The study population includes both male and female subjects, aged 30 years and older, who meet specific criteria for inclusion. Participants were selected based on their previous involvement in related studies or their naivety to the ND0612 treatment, with a requirement for stability in their anti-Parkinson's medications for at least 30 days prior to the study. The trial includes individuals who are able to administer the subcutaneous infusion independently or with assistance. Participants are required to have a predictable pattern of "OFF" periods and a good response to levodopa. The study population is characterized by a diverse range of individuals, including those who may be considered vulnerable. Lifestyle factors such as diet and physical activity are not specified, but female participants must adhere to strict contraceptive measures if of childbearing potential. The trial aims to assess the long-term safety and tolerability of continuous subcutaneous infusion of ND0612.
Plans and Procedures
The clinical trial is designed to evaluate the long-term safety and tolerability of **ND0612**, a solution containing **carbidopa** and **levodopa**, administered as a continuous subcutaneous infusion in patients with advanced **Parkinson's disease**. This is a Phase 4, multicenter, international, open-label study. The trial will span approximately 12 months, with the primary endpoint focusing on the safety and tolerability of the treatment. Secondary endpoints include assessments of suicidal behavior, impulsive compulsive behavior, sleepiness, vital signs, laboratory data, ECG parameters, physical examination, medication use, and changes in daily "ON" and "OFF" times, among others.
Participants will undergo a series of study visits, beginning with a screening visit to determine eligibility based on specific inclusion criteria, such as a diagnosis consistent with the UK Brain Bank Criteria and a stable medication regimen. The screening period may last up to 40 days. Following successful screening, participants will enter the treatment phase, which includes regular follow-up visits to monitor safety and efficacy parameters. The end-of-study visit will conclude the trial, assessing the overall impact of the treatment over the 12-month period.
Participant involvement is expected to last for the entire duration of the trial, approximately 12 months. However, conditions that may lead to early termination from the study include significant medical, psychiatric, or laboratory abnormalities deemed unsafe by the investigator, or non-compliance with study procedures. The trial aims to provide comprehensive data on the long-term use of ND0612 in managing advanced Parkinson's disease, contributing valuable insights into its safety profile and therapeutic potential.
Treatment
The clinical trial involves the administration of **ND0612**, a pharmaceutical product developed by NeuroDerm Ltd. ND0612 is a **solution for infusion** in an administration system, specifically designed for continuous subcutaneous infusion. The active substances in ND0612 are **carbidopa** and **levodopa**, both of which are of chemical origin. The solution is delivered via an infusion pump system, which has been certified with a CE mark by KIWA CERMET ITALIA S.p.A. The maximum daily dose of ND0612 is 720 mg, with a total maximum dose of 2,210,544 mg over a treatment period of up to 102 days. The administration route is subcutaneous, and the treatment is not formulated for pediatric use.
In this study, ND0612 is the experimental medication, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial is designed to assess the long-term safety and tolerability of the continuous subcutaneous infusion of ND0612 in subjects with advanced **Parkinson's Disease**. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.
Efficacy
Efficacy in this clinical trial will be assessed through a series of secondary endpoints designed to evaluate various aspects of treatment impact on subjects with advanced Parkinson's Disease. These endpoints include changes in daily "ON" time without troublesome dyskinesia and daily "OFF" time from baseline to the 12-month visit, as recorded in home "ON/OFF" diaries. Additionally, the trial will measure changes in the total daily dose of oral levodopa/dopa decarboxylase inhibitor (LD/DDI) from baseline to the 12-month visit, and the proportion of responders at the 12-month visit based on daily "OFF" time recorded in home diaries.
Further assessments will include changes in Parkinson's Disease Questionnaire-39 (PDQ-39) scores, EQ-5D-5L scores, and Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (motor score) from baseline to the 12-month visit. The trial will also evaluate changes in Clinical Global Impression-Severity (CGI-Severity) and Clinical Global Impression-Improvement (CGI-Improvement) scores, as well as Subject Global Impression-Improvement (SGI-Improvement) scores over the same period. The Parkinson's Disease Sleep Scale (PDSS) total score will be assessed from baseline to the 12-month visit.
Additional efficacy parameters include changes from baseline to month 12 in the percentage of "OFF" time and percentage of 'Good' ON during the first 3 hours since the subject is awake after 06:00 (6 am), and changes in ND0612 total dose. The proportion of patients who reduced ND0612 total dose at any time during the study will also be evaluated. These efficacy assessments will be conducted using validated scales and patient-reported outcomes, ensuring a comprehensive evaluation of the treatment's impact on the subjects' condition over the course of the trial.
Inclusion and Exclusion Criteria
Inclusion Criteria
- To be eligible for study entry subjects in Cohort 1 (previously completed the treatment period in protocol ND0612H-006 within one month prior to enrolling to ND0612H-012) must satisfy all of the following criteria: 1.Subject is able to, and has signed an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).
- Cohort 2: 5.Subjects must be stable on their anti-PD medications for at least 30 days before Day 1.
- Cohort 2: 7.Must have a minimum of 2 hrs of “OFF” time per day with predictable early morning “OFF” periods as estimated by the subject.
- Cohort 2: 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.
- Cohort 2: 9.Mini Mental State Examination (MMSE) score ≥ 26.
- Cohort 2: 10.No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or noncompliant in the study.
- Cohort 2: 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 nonlactating 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.
- Cohort 2: 12.Willing and able to administer the SC infusion alone or with the assistance of a study partner after a screening period up to 40 days and willing and able to comply with study requirements.
- Cohort 2: 13. Subjects should have a named study partner.
- Cohort 2: 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.
- Cohort 1: 2.Subject has completed the treatment period of study ND0612H-006 not more than one month prior to enrolling in ND0612H-012.
- Cohort 1: 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.
- To be eligible for study entry subjects in Cohort 2 (ND0612 naïve subjects and subjects who completed treatment in a ND0612 clinical study more than one month before screening) must satisfy all of the following criteria: 1.Male and female PD subjects of any race aged at least 30 years who sign an IRB/EC-approved ICF.
- Cohort 2: 2.PD diagnosis consistent with the UK Brain Bank Criteria.
- Cohort 2: 3.Modified Hoehn & Yahr scale in “ON” state of stage ≤3.
- Cohort 2: 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.
Exclusion Criteria
- Subjects in Cohort 1 and Cohort 2 will be excluded from the study if one or more of the following criteria listed below are applicable. 1.Previously unable to tolerate ND0612 and/or have experienced intolerable adverse drug reactions associated with its use, regardless of the dosing regimen administered.
- For Cohort 2 the following exclusion criteria apply: 1.Atypical or secondary parkinsonism.
- Cohort 2: 2.Acute psychosis or hallucinations in past 6 months.
- Cohort 2: 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.
- Cohort 2: 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 treatment.
- Cohort 2: 5. Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the screening visit.
- Cohort 2: 6. Prior neurosurgical procedure for PD, or Duodopa treatment
- Cohort 2: 7. Subjects with a history of drug abuse or alcoholism within the past 12 months.
- Cohort 2: 8. Clinically significant ECG rhythm abnormalities.
- Cohort 2: 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.
- Cohort 2: 10. Current participation in a clinical trial with an investigational product or past participation within the last 30 days before Day 1.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 18 Oct 2016 | 3 |
 France | Not Recruiting | 18 Oct 2016 | 9 |
 Italy | Not Recruiting | 18 Oct 2016 | 16 |
 Poland | Not Recruiting | 18 Oct 2016 | 14 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ND0612 | Test | SOLUTION FOR INFUSION IN ADMINISTRATION SYSTEM | SUBCUTANEOUS | 720 | 102 | PRD3503373 |