A Phase 2a Study Followed to Evaluate the Safety, Tolerability and Levodopa Pharmacokinetics in Levodopa-treated Parkinson's Disease Patients Receiving ND0612

Study Overview
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Brief Summary
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This phase 2a randomized double blind placebo controlled, in 30 Parkinson's disease (PD) subjects who are treated with oral levodopa/carbidopa (LD/CD) and suffer from motor fluctuations. The aim of the study is to determine the safety, tolerability, the levodopa pharmacokinetics, the need for oral LD dose adjustment and the usability of the ambulatory drug delivery pump following repeated dosing of ND0612 in a conventional home setting in Parkinson's disease patients. Safety and tolerability, pharmacokinetic profile of levodopa and carbidopa, pump usability and the potential clinical effect of ND0612 will be explored in subjects with PD and motor fluctuations.

Official Title
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A Phase 2a Multicentre Randomized Double Blind Placebo Controlled Study Followed by an Open Label Period, to Evaluate the Safety, Tolerability and Levodopa Pharmacokinetics in Levodopa-treated Parkinson's Disease Patients With Motor Fluctuations, Administered With Repeated Continuous Subcutaneous ND0612

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Levodopa and carbidopa
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women with idiopathic Parkinson's disease Subjects must experience motor fluctuations associated with LD/CD dosing Modified Hoehn and Yahr stage < 5 Subjects must be taking optimized and stable levodopa/dopa decarboxylase inhibitor therapy Subjects who are treated with dopaminergic agonists and other anti-PD drugs should be on stable doses Women must be postmenopausal, surgically sterilized, or using adequate birth control. Women of childbearing potential must have a negative pregnancy test (serum beta-HCG) at screening. Subjects must be age 30 or older. Subjects must be willing and able to give informed consent Exclusion Criteria: Subjects treated with entacapone, tolcapone, stalevo or controlled release formulation of levodopa/carbidopa. Subjects with a clinically significant or unstable medical or surgical condition History of melanoma or significant skin disorders Subjects with significant cognitive impairment Subjects treated with unstable doses of dopaminergic agonists, anticholinergics, Monoamine oxidase (MAO)-B inhibitors, or antipsychotics Subjects with clinically significant psychiatric illness Subjects with a history of alcohol or substance abuse Subjects who have taken experimental medications within 60 days prior to baseline. Subject who have undergone a neurosurgical intervention for Parkinson's disease (e.g., pallidotomy, thalamotomy, transplantation and deep brain stimulation). Subjects with severe disabling dyskinesias. Subjects with hearing, visual or motor impairments that prevent them from using the pump or reacting effectively to errors

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ND0612<br>levodopa and carbidopa solution | Drug: Levodopa and carbidopa<br>* Subcutaneous continuous administration<br>* Other names: Levodopa and carbidopa or saline;|
| Placebo Comparator: Placebo<br>Saline | Drug: Placebo<br>* Subcutaneous continuous administration<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | 1. Incidence and frequency of adverse events, of dopaminergic adverse events 2. Adverse events reporting related to the ND0612 subcutaneous administration, Draize score 3. Vital signs, physical exam, Laboratory measurements | 14 days | 
| Levodopa pharmacokinetics (LD PK) | LD PK parameters: Cmax, Area under the Curve (AUC), T>1000ng/ml, through levels at baseline and during treatment at 14 days. | 1hr and 2hr predose, 0h, 0.5 hr, 1hr, 1.5hr, 2hr, 3hr, 4hr, 5hr, 6hr, 7hr, 8hr, 9hr and 10hr hours post oral LD dose | 
| Tolerability | Withdrawal rates and discontinuations due to adverse events | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LD dose adjustment | Change in oral LD total daily dose, change in number of oral LD doses during the first 2 weeks, use of rescue therapy during the third week. | 14 days | 
| Pump Usability | Simulated usability study, formative Pump usability evaluation. Human factor study. Training on the use of the pump will be performed and questionnaire will be filled to assess the ease of use of the pump and the efficiency of the training. | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Motor fluctuations, levodopa pharmacokinetics, levodopa and carbidopa solution, continuous subcutaneous delivery, Patch-pump