A Phase 2a Study Followed to Evaluate the Safety, Tolerability and Levodopa Pharmacokinetics in Levodopa-treated Parkinson's Disease Patients Receiving ND0612 (ND0612/003)

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Levodopa and carbidopa; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Petah Tikva, Israel
    • Rabin Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women with idiopathic Parkinson's disease
2. Subjects must experience motor fluctuations associated with LD/CD dosing
3. Modified Hoehn and Yahr stage < 5
4. Subjects must be taking optimized and stable levodopa/dopa decarboxylase inhibitor therapy
5. Subjects who are treated with dopaminergic agonists and other anti-PD drugs should be on stable doses
6. 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.
7. Subjects must be age 30 or older.
8. Subjects must be willing and able to give informed consent

Exclusion Criteria:

1. Subjects treated with entacapone, tolcapone, stalevo or controlled release formulation of levodopa/carbidopa.
2. Subjects with a clinically significant or unstable medical or surgical condition
3. History of melanoma or significant skin disorders
4. Subjects with significant cognitive impairment
5. Subjects treated with unstable doses of dopaminergic agonists, anticholinergics, Monoamine oxidase (MAO)-B inhibitors, or antipsychotics
6. Subjects with clinically significant psychiatric illness
7. Subjects with a history of alcohol or substance abuse
8. Subjects who have taken experimental medications within 60 days prior to baseline.
9. Subject who have undergone a neurosurgical intervention for Parkinson's disease (e.g., pallidotomy, thalamotomy, transplantation and deep brain stimulation).
10. Subjects with severe disabling dyskinesias.
11. Subjects with hearing, visual or motor impairments that prevent them from using the pump or reacting effectively to errors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline	Drug: Placebo; Subcutaneous continuous administration; Other Names: Saline
Experimental: ND0612; levodopa and carbidopa solution	Drug: Levodopa and carbidopa; Subcutaneous continuous administration; Other Names: Levodopa and carbidopa or saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NeuroDerm Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2014
• Primary Completion (Actual): April 26, 2015
• Study Completion (Actual): April 26, 2015

Study Registration Dates

• First Submitted: June 9, 2013
• First Submitted That Met QC Criteria: June 19, 2013
• First Posted (Estimated): June 21, 2013

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Motor fluctuations; levodopa pharmacokinetics; levodopa and carbidopa solution; continuous subcutaneous delivery; Patch-pump
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa
• Other Study ID Numbers: ND0612/003