A Safety, Tolerability and Levodopa Pharmacokinetics Study of Repeated ND0612 in Parkinson's Disease Patients (ND0612/003)

A Phase IIa Multicenter, 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 Subcutaneous ND0612

This is a randomized, placebo-controlled, double-blind, 2-period study evaluating the safety and pharmacokinetics (PK) of ND0612 in Parkinson's disease (PD) patients on an optimized oral levodopa (LD) regimen and experiencing ≥2 h/day of OFF time. Safety and tolerability, PK profile, 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: ND0612; Drug: Placebo; Drug: Entacapone

Detailed Description

During Period 1, patients continued on their current standard of care (SoC) levodopa/carbidopa (LD/CD) and were randomized at 2:1 ratio to 14 days of adjunct treatment with ND0612 (daily LD/CD dose of 270/63 mg) or placebo infusion. During Period 2, patients were randomized to receive 7 days open-label treatment with ND0612 or ND0612 plus oral entacapone. Patients then entered a 4-week safety follow-up period.

• 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 PD whose diagnosis was confirmed by presence of at least two of the cardinal signs (resting tremor, bradykinesia, rigidity) and lacking any other known or suspected cause of parkinsonism.
2. Patients who experienced motor fluctuations averaging at least two hours daily in the "OFF" state during the waking hours (including morning akinesia), corresponding to the end-of-dose deterioration phenomenon ("wearing off") confirmed by the baseline home diaries.
3. Modified Hoehn and Yahr stage < 5 in the "OFF" state.
4. Patients who were taking optimized LD/decarboxylase inhibitor therapy (based on the investigator's judgment) that was stable for at least 14 days prior to baseline. Patients were to receive at least three daily doses of LD (which could include a bedtime dose) with at least three hours between doses.
5. Patients treated with dopaminergic agonists and other anti-PD drugs were to be on stable doses for at least 30 days prior to baseline and those doses were to remain constant throughout the study period.
6. Women who were postmenopausal, surgically sterilized, or using adequate birth control. Women of childbearing potential were to have a negative pregnancy test (beta human chorionic gonadotropin [hCG] serum) at screening.
7. Patients between the ages of 30 and 80.
8. Patients willing and able to give informed consent.
9. Patients and/or caregivers able to understand and follow instructions for use of SC delivery pump.
10. Patients who demonstrated the ability to keep accurate diaries of PD symptoms (ON-OFF diaries).

Exclusion Criteria:

1. Patients treated with controlled release formulation of LD/CD. (Note: Patients treated with Entacapone, Tolcapone, or Stalevo were allowed to participate in Period 1 but were excluded from Period 2 participation)
2. Patients with a clinically significant or unstable medical or surgical condition which would preclude safe and complete study participation. Such conditions may include gastrointestinal, cardiovascular, pulmonary, hepatic, renal, or metabolic diseases or malignancies as determined by medical history, physical exam, laboratory tests, or ECG.
3. History of melanoma or significant skin disorders.
4. Patients with significant cognitive impairment as defined by a MMSE score of < 25.
5. Patients treated with dopaminergic agonists, anticholinergics, monoamine oxidase (MAO)-B inhibitors, or antipsychotics that need dose adjustment in the 30 days prior to Study Baseline.
6. Patients with clinically significant psychiatric illness, including major depression (according to Diagnostic and Statistical Manual of Mental Disorders [DSM] IV criteria for major depressive episode) or other problems that might compromise their ability to provide consent or participate fully in the study.
7. Patients with a history of alcohol or substance abuse within the past two years.
8. Patients who have taken experimental medications within 60 days prior to baseline.
9. Patients who have undergone a neurosurgical intervention for PD (e.g. pallidotomy, thalamotomy, transplantation, or deep brain stimulation procedures).
10. Patients with severe disabling dyskinesias.
11. Patients 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1. ND0612; A 24h SC infusion of levodopa/carbidopa 270/63 mg daily in addition to the current standard of care treatment for 14 days	Drug: ND0612; Subcutaneous infusion via CRONO ND pump; Other Names: Levodopa and carbidopa SC solution
Placebo Comparator: Period 1. Placebo; A 24h SC infusion of saline in addition to the current standard of care treatment for 14 days	Drug: Placebo; Subcutaneous infusion via CRONO ND pump; Other Names: Saline
Experimental: Period 2. ND0612; A 24h SC infusion of levodopa/carbidopa 270/63 mg daily in addition to the current standard of care treatment for 7 days	Drug: ND0612; Subcutaneous infusion via CRONO ND pump; Other Names: Levodopa and carbidopa SC solution
Experimental: Period 2. ND0612 + Entacapone; A 24h SC infusion of levodopa/carbidopa 270/63 mg daily in addition to the current standard of care treatment + Entacapone 200 mg 3 times/day (every 6 hours during waking hours) for 7 days	Drug: ND0612; Subcutaneous infusion via CRONO ND pump; Other Names: Levodopa and carbidopa SC solution; Drug: Entacapone; 200 mg oral tablet

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.
• Investigators: Study Director: Senior Medical Director, 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 (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Motor fluctuations; levodopa pharmacokinetics; levodopa and carbidopa solution; continuous subcutaneous delivery; ambulatory infusion pump
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Amino Acids, Peptides, and Proteins; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Inorganic Chemicals; Chlorine Compounds; Amino Acids; Catechols; Phenols; Benzene Derivatives; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Catecholamines; Dihydroxyphenylalanine; Sodium Compounds; Chlorides; Hydrochloric Acid; Tyrosine; Levodopa; Sodium Chloride; entacapone
• Other Study ID Numbers: ND0612/003