A Phase I/IIa Study of Safety, Tolerability and Plasma Concentration of Subcutaneous Continuously-delivered Levodopa/Carbidopa Solution (ND0612) in PD Patients

Study Overview
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Brief Summary
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In this Phase I/IIa study, the effect of continuous subcutaneous administration of LD/CD solution (ND0612) on the safety and PK profile of LD will be examined.

Detailed Description
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Design: single center, double-blind, randomized, placebo-controlled, crossover study. Study Drug: Subcutaneous (SC), ND0612 (LD/CD solution) or placebo (saline) to be administered via a continuously via the CRONO Five SC pump. A 1-week washout period will apply between the treatments. Population: Eight (8) PD subjects.

Official Title
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A Phase I/IIa, Single Dose, Single-centre, Randomized, Crossover, Double-blind, Placebo-controlled Study Evaluating Safety, Tolerability and Levodopa Plasma Concentration Following Administration of Subcutaneous Continuously-delivered Levodopa/Carbidopa Solution (ND0612) in PD Patients

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: levodopa and carbidopa solution for SC administration
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main 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 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. Main Exclusion Criteria: Subjects with a clinically significant or unstable medical or surgical condition Subjects with clinically significant psychiatric illness. Pre-menopausal women, not using birth control method. 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).

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: levodopa and carbidopa<br>levodopa and carbidopa solution | Drug: levodopa and carbidopa solution for SC administration<br> <br> |
| Placebo Comparator: placebo to levodopa and carbidopa<br>saline | Drug: Placebo<br> <br> * Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and frequency of adverse events | Incidence and frequency of adverse events Adverse events reporting related to the ND0612 application, local safety score | up to 8 weeks | 
| Withdrawal rate | Withdrawal rates and discontinuations due to adverse events | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LD Half life (t½ ), time of LD plasma concentrations maintained above 1000 ng/ml, trough levels, Cmax, Tmax and AUC | LD PK profile after oral LD dosing administered with or without ND0612: | Up to 2 days |